id miRNA_symbol miRBase_mature_ID miRBase_ID RNA Category Gene_Symbol Pathway Action_Mode Organism Tissue PMID tax_id geneid Synonyms Links chromosome map_location Description type_of_gene Full_name_from_nomenclature_authority Other_designations Description 1 let-7 hsa-let-7a-5p,hsa-let-7b-5p,hsa-let-7d-5p,hsa-let-7e-5p,hsa-let-7f-5p,hsa-let-7g-5p,hsa-let-7i-5p,hsa-let-7a-3p,hsa-let-7b-3p,hsa-let-7d-3p,hsa-let-7e-3p,hsa-let-7f-1-3p,hsa-let-7f-2-3p,hsa-let-7g-3p,hsa-let-7i-3p,hsa-let-7a-2-3p,hsa-let-7c-5p, MIMAT0000062,MIMAT0000063,MIMAT0000065,MIMAT0000066,MIMAT0000067,MIMAT0000414,MIMAT0000415,MIMAT0004481,MIMAT0004482,MIMAT0004484,MIMAT0004485,MIMAT0004486,MIMAT0004487,MIMAT0004584,MIMAT0004585,MIMAT0010195,MIMAT0000064 miRNA ain-1 autophagy down Caenorhabditis elegans 23619095 6239 181719 - - X - Protein AIN-1 protein-coding - Loss of autophagy activity suppresses developmental defects caused by partially impaired silencing of miRNA targets including the let-7 family and lsy-6. The C. elegans GW182 homolog AIN-1 is itself selectively degraded by autophagy and colocalizes with the p62 homolog SQST-1 in autophagy mutants. Thus, autophagy activity modulates miRNA-mediated gene silencing and degrades a core miRISC component. 2 lsy-6 cel-lsy-6-3p,cel-lsy-6-5p MIMAT0000749,MIMAT0031896 miRNA ain-1 autophagy down Caenorhabditis elegans 23619095 6239 181719 - - X - Protein AIN-1 protein-coding - Loss of autophagy activity suppresses developmental defects caused by partially impaired silencing of miRNA targets including the let-7 family and lsy-6. The C. elegans GW182 homolog AIN-1 is itself selectively degraded by autophagy and colocalizes with the p62 homolog SQST-1 in autophagy mutants. Thus, autophagy activity modulates miRNA-mediated gene silencing and degrades a core miRISC component. 3 miR-34 cel-miR-34-5p,cel-miR-34-3p MIMAT0000005,MIMAT0015093 miRNA atg-9 autophagy down Caenorhabditis elegans 22081425 6239 178561 - - V - Protein ATG-9 protein-coding - MiR-34 modulates Caenorhabditis elegans lifespan via repressing the autophagy gene atg9. 4 miR-34 cel-miR-34-3p,cel-miR-34-3p MIMAT0000005,MIMAT0015093 miRNA cep-1 apoptosis Caenorhabditis elegans 19421141 6239 172616 - - I - Protein CEP-1 protein-coding - MiRNA expression is also affected by DNA damaging agents, such as radiation. In particular, mammalian miR-34 is upregulated by p53 in response to radiation, but little is known about the role of this miRNA in vivo. Here we show that Caenorhabditis elegans with loss-of-function mutations in the mir-34 gene have an abnormal cellular survival response to radiation; these animals are highly radiosensitive in the soma and radioresistant in the germline. These findings show a role for mir-34 in both apoptotic and non-apoptotic cell death in vivo, much like that of cep-1, the C. elegans p53 homolog. 5 miR-14 dme-miR-14-5p,dme-miR-14-3p MIMAT0020798,MIMAT0000120 miRNA IP3K2 autophagy Drosophila melanogaster salivary gland cell 25306920 7227 Here, we identify the microRNA miR-14 as being both necessary and sufficient for autophagy during developmentally regulated cell death in Drosophila. Loss of miR-14 prevented induction of autophagy during salivary gland cell death, but had no effect on starvation-induced autophagy in the fat body. Moreover, misexpression of miR-14 was sufficient to prematurely induce autophagy in salivary glands, but not in the fat body. Importantly, miR-14 regulates this context-specific autophagy through its target, inositol 1,4,5-trisphosphate kinase 2 (ip3k2), thereby affecting inositol 1,4,5-trisphosphate (IP3) signaling and calcium levels during salivary gland cell death. 6 hsr omega transcripts http://lncrna.com/hsromegatranscripts/ lncRNA caspases apoptosis Drosophila melanogaster eye disc cells 19737742 7227 39753 0736/01|1065/03|CG12284|D-IAP1|D-iap1|DIAP|DIAP I|DIAP-1|DIAP1|DIAPI|Diap|Diap-1|Diap-1/Th|Diap1|Diap2|Dmel\CG12284|E(rpr)3-1|IAP|IAP1|Iap1|S048915|TH|dIAP|dIAP-1|dIAP1|dIap1|diap|diap 1|diap-1|diap1|diap1/thread|l(3)72CDe|l(3)72Dc|l(3)S030605|l(3)S030605b|l(3)S106503|l(3)j5C8 FLYBASE:FBgn0260635 3L 72C1-72D1|3-43.2 cM thread protein-coding thread diaphanous-related formin The large nucleus limited noncoding hsromega-n RNA of Drosophila melanogaster is known to associate with a variety of heterogeneous nuclear RNA-binding proteins (hnRNPs) and certain other RNA-binding proteins to assemble the nucleoplasmic omega speckles. In this article, we show that RNAi-mediated depletion of this noncoding RNA dominantly suppresses apoptosis, in eye and other imaginal discs, triggered by induced expression of Rpr, Grim, or caspases (initiator as well as effector), all of which are key regulators/effectors of the canonical caspase-mediated cell death pathway. We also show, for the first time, a genetic interaction between the noncoding hsromega transcripts and the c-Jun N-terminal kinase (JNK) signaling pathway since downregulation of hsromega transcripts suppressed JNK activation. In addition, hsromega-RNAi also augmented the levels of Drosophila Inhibitor of Apoptosis Protein 1 (DIAP1) when apoptosis was activated. 7 hsr omega transcripts http://lncrna.com/hsromegatranscripts/ lncRNA grim apoptosis Drosophila melanogaster eye disc cells 19737742 7227 40014 BcDNA:RE28551|CG4345|Dmel\CG4345|GRIM|Grim|gri|grm FLYBASE:FBgn0015946 3L 75C4-75C4 CG4345 gene product from transcript CG4345-RA protein-coding - diaphanous-related formin The large nucleus limited noncoding hsromega-n RNA of Drosophila melanogaster is known to associate with a variety of heterogeneous nuclear RNA-binding proteins (hnRNPs) and certain other RNA-binding proteins to assemble the nucleoplasmic omega speckles. In this article, we show that RNAi-mediated depletion of this noncoding RNA dominantly suppresses apoptosis, in eye and other imaginal discs, triggered by induced expression of Rpr, Grim, or caspases (initiator as well as effector), all of which are key regulators/effectors of the canonical caspase-mediated cell death pathway. We also show, for the first time, a genetic interaction between the noncoding hsromega transcripts and the c-Jun N-terminal kinase (JNK) signaling pathway since downregulation of hsromega transcripts suppressed JNK activation. In addition, hsromega-RNAi also augmented the levels of Drosophila Inhibitor of Apoptosis Protein 1 (DIAP1) when apoptosis was activated. 8 hsr omega transcripts http://lncrna.com/hsromegatranscripts/ lncRNA RpII215 apoptosis Drosophila melanogaster 17536179 7227 32100 5|8WG16|CG1554|CTD|Dmel\CG1554|H5|II|IIo|L5|POL|Pol II|Pol II CTD|Pol II Ser5P|Pol II Ser5p|Pol II0[ser2]|Pol II0[ser5]|Pol II[ser2]|Pol IIa|Pol IIo|Pol IIo[Ser2]|Pol IIo[ser2]|Pol IIo[ser5]|Pol-IIa|PolII|PolIIa|PolIIo|PolIIo[ser2]|PolIIo[ser5]|RNA Pol II|RNA Pol II CTD|RNA PolI 215|RNA PolII|RNA pol II|RNA pol IIo|RNA polII|RNA-PolII|RNAP|RNAP II|RNAP II LS|RNAPII|RNAPII0|RNApol2|RNApolII|RPB1|RPII215|RpII|Rpb1|Rpll215|Ser5-P Pol II|Ubl|alphaPol IIo[ser2]|dRPB1|dRpb1|l(1)10Ca|l(1)DC912|l(1)DF912|l(1)G0040|l(1)L5|pol II|polII|rpII1 FLYBASE:FBgn0003277 X 10C6-10C6|1-35.66 cM RNA polymerase II 215kD subunit protein-coding RNA polymerase II 215kD subunit Studies in our laboratory also reveal that absence or reduced levels of the developmentally active as well as stress induced non-coding hsr omega transcripts, which are known to sequester diverse hnRNPs and related nuclear RNA-binding proteins,block induced apoptosis in Drosophila. 9 hsr omega transcripts http://lncrna.com/hsromegatranscripts/ lncRNA rpr apoptosis Drosophila melanogaster eye disc cells 19737742 7227 40015 CG4319|Dmel\CG4319|RPR|Rpr|anon-WO0162936.19|rp FLYBASE:FBgn0011706 3L 75C6-75C6 reaper protein-coding reaper diaphanous-related formin The large nucleus limited noncoding hsromega-n RNA of Drosophila melanogaster is known to associate with a variety of heterogeneous nuclear RNA-binding proteins (hnRNPs) and certain other RNA-binding proteins to assemble the nucleoplasmic omega speckles. In this article, we show that RNAi-mediated depletion of this noncoding RNA dominantly suppresses apoptosis, in eye and other imaginal discs, triggered by induced expression of Rpr, Grim, or caspases (initiator as well as effector), all of which are key regulators/effectors of the canonical caspase-mediated cell death pathway. We also show, for the first time, a genetic interaction between the noncoding hsromega transcripts and the c-Jun N-terminal kinase (JNK) signaling pathway since downregulation of hsromega transcripts suppressed JNK activation. In addition, hsromega-RNAi also augmented the levels of Drosophila Inhibitor of Apoptosis Protein 1 (DIAP1) when apoptosis was activated. 10 hsr omega transcripts http://lncrna.com/hsromegatranscripts/ lncRNA th apoptosis up Drosophila melanogaster eye disc cells 19737742 7227 39753 0736/01|1065/03|CG12284|D-IAP1|D-iap1|DIAP|DIAP I|DIAP-1|DIAP1|DIAPI|Diap|Diap-1|Diap-1/Th|Diap1|Diap2|Dmel\CG12284|E(rpr)3-1|IAP|IAP1|Iap1|S048915|TH|dIAP|dIAP-1|dIAP1|dIap1|diap|diap 1|diap-1|diap1|diap1/thread|l(3)72CDe|l(3)72Dc|l(3)S030605|l(3)S030605b|l(3)S106503|l(3)j5C8 FLYBASE:FBgn0260635 3L 72C1-72D1|3-43.2 cM thread protein-coding thread diaphanous-related formin The large nucleus limited noncoding hsromega-n RNA of Drosophila melanogaster is known to associate with a variety of heterogeneous nuclear RNA-binding proteins (hnRNPs) and certain other RNA-binding proteins to assemble the nucleoplasmic omega speckles. In this article, we show that RNAi-mediated depletion of this noncoding RNA dominantly suppresses apoptosis, in eye and other imaginal discs, triggered by induced expression of Rpr, Grim, or caspases (initiator as well as effector), all of which are key regulators/effectors of the canonical caspase-mediated cell death pathway. We also show, for the first time, a genetic interaction between the noncoding hsromega transcripts and the c-Jun N-terminal kinase (JNK) signaling pathway since downregulation of hsromega transcripts suppressed JNK activation. In addition, hsromega-RNAi also augmented the levels of Drosophila Inhibitor of Apoptosis Protein 1 (DIAP1) when apoptosis was activated. 11 bantam dme-bantam-5p,dme-bantam-3p MIMAT0020823,MIMAT0000365 miRNA W apoptosis down Drosophila melanogaster wing disc 12679032 7227 40009 CG5123|Dmel\CG5123|HID|Hid|Hid1|hid|hid1|his|l(3)05014 FLYBASE:FBgn0003997 3L 75C1-75C1 Wrinkled protein-coding Wrinkled CG5123-PA|W-PA|head invol Bantam expression is temporally and spatially regulated in response to patterning cues. bantam microRNA simultaneously stimulates cell proliferation and prevents apoptosis. We identify the pro-apoptotic gene hid as a target for regulation by bantam miRNA, providing an explanation for bantam's anti-apoptotic activity. 12 miR-11 dme-miR-11-3p,dme-miR-11-5p MIMAT0000116,MIMAT0020793 miRNA rpr apoptosis Drosophila melanogaster embryos 22095284 7227 40015 CG4319|Dmel\CG4319|RPR|Rpr|anon-WO0162936.19|rp FLYBASE:FBgn0011706 3L 75C6-75C6 reaper protein-coding reaper CG5123-PA|W-PA|head invol MiR-6/11 functions through regulation of the proapoptotic genes, reaper (rpr), head involution defective(hid), grim and sickle (skl). Upregulation of these proapoptotic genes is responsible for the elevated apoptosis and the CNS defects in the mutants. 13 miR-11 dme-miR-11-3p,dme-miR-11-5p MIMAT0000116,MIMAT0020793 miRNA skl apoptosis Drosophila melanogaster embryos 22095284 7227 40016 BcDNA:RE14076|CG13701|Dmel\CG13701|Skl|meph|veto FLYBASE:FBgn0036786 3L 75C6-75C6 sickle protein-coding sickle CG13701-PA|mephisto|skl-P MiR-6/11 functions through regulation of the proapoptotic genes, reaper (rpr), head involution defective(hid), grim and sickle (skl). Upregulation of these proapoptotic genes is responsible for the elevated apoptosis and the CNS defects in the mutants. 14 miR-11 dme-miR-11-3p,dme-miR-11-5p MIMAT0000116,MIMAT0020793 miRNA W apoptosis Drosophila melanogaster embryos 22095284 7227 40009 CG5123|Dmel\CG5123|HID|Hid|Hid1|hid|hid1|his|l(3)05014 FLYBASE:FBgn0003997 3L 75C1-75C1 Wrinkled protein-coding Wrinkled CG5123-PA|W-PA|head invol MiR-6/11 functions through regulation of the proapoptotic genes, reaper (rpr), head involution defective(hid), grim and sickle (skl). Upregulation of these proapoptotic genes is responsible for the elevated apoptosis and the CNS defects in the mutants. 15 miR-14 dme-miR-14-5p,dme-miR-14-3p MIMAT0020798,MIMAT0000120 miRNA Ice apoptosis down Drosophila melanogaster larvae and adult 12725740 7227 43514 CG7788|DRICE|Dmel\CG7788|DrICE|DrIce|Drice|Drive|ICE|caspase 3|crice|drICE|drIce|drice|ice FLYBASE:FBgn0019972 3R 99C1-99C1 CG7788 gene product from transcript CG7788-RA protein-coding - CG7788-PA|Ice-PA|caspase- Mir-14 mutants have elevated levels of the apoptotic effector caspase Drice, suggesting one potential site of action. Mir-14 also regulates fat metabolism. 16 miR-263a dme-miR-263a-5p,dme-miR-263a-3p MIMAT0000319,MIMAT0020799 miRNA apoptosis Drosophila melanogaster 20563308 7227 MiR-263a/b are members of a conserved family of microRNAs that are expressed in peripheral sense organs across the animal kingdom. Here we present evidence that miR-263a and miR-263b play a role in protecting Drosophila mechanosensory bristles from apoptosis by down-regulating the pro-apoptotic gene head involution defective. 17 miR-263b dme-miR-263a-5p,dme-miR-263a-3p MIMAT0000319,MIMAT0020799 miRNA apoptosis Drosophila melanogaster 20563308 7227 MiR-263a/b are members of a conserved family of microRNAs that are expressed in peripheral sense organs across the animal kingdom. Here we present evidence that miR-263a and miR-263b play a role in protecting Drosophila mechanosensory bristles from apoptosis by down-regulating the pro-apoptotic gene head involution defective. 18 miR-6 dme-mir-6-5p,dme-miR-6-3p MIMAT0020787,MIMAT0000111 miRNA rpr apoptosis Drosophila melanogaster embryos 22095284 7227 40015 CG4319|Dmel\CG4319|RPR|Rpr|anon-WO0162936.19|rp FLYBASE:FBgn0011706 3L 75C6-75C6 reaper protein-coding reaper CG5123-PA|W-PA|head invol MiR-6/11 functions through regulation of the proapoptotic genes, reaper (rpr), head involution defective(hid), grim and sickle (skl). Upregulation of these proapoptotic genes is responsible for the elevated apoptosis and the CNS defects in the mutants. 19 miR-6 dme-mir-6-5p,dme-miR-6-3p MIMAT0020787,MIMAT0000111 miRNA skl apoptosis Drosophila melanogaster embryos 22095284 7227 40016 BcDNA:RE14076|CG13701|Dmel\CG13701|Skl|meph|veto FLYBASE:FBgn0036786 3L 75C6-75C6 sickle protein-coding sickle CG13701-PA|mephisto|skl-P MiR-6/11 functions through regulation of the proapoptotic genes, reaper (rpr), head involution defective(hid), grim and sickle (skl). Upregulation of these proapoptotic genes is responsible for the elevated apoptosis and the CNS defects in the mutants. 20 miR-6 dme-mir-6-5p,dme-miR-6-3p MIMAT0020787,MIMAT0000111 miRNA W apoptosis Drosophila melanogaster embryos 22095284 7227 40009 CG5123|Dmel\CG5123|HID|Hid|Hid1|hid|hid1|his|l(3)05014 FLYBASE:FBgn0003997 3L 75C1-75C1 Wrinkled protein-coding Wrinkled CG5123-PA|W-PA|head invol MiR-6/11 functions through regulation of the proapoptotic genes, reaper (rpr), head involution defective(hid), grim and sickle (skl). Upregulation of these proapoptotic genes is responsible for the elevated apoptosis and the CNS defects in the mutants. 21 miR-8 dme-miR-8-5p,dme-miR-8-3p MIMAT0020791,MIMAT0000113 miRNA Gug apoptosis Drosophila melanogaster brain 17923093 7227 46156 Atro|CG6964|Dmel\CG6964|GUG|atro|gug|l(3)01323|l(3)03928|l(3)S146907|l(3)j5A3|l(3)rO116 FLYBASE:FBgn0010825 3L 66C13-66D1|3-26 cM Grunge protein-coding Grunge CG6964-PA|CG6964-PB|CG696 MiR-8 mutant phenotypes are attributable to elevated atrophin activity, resulting in elevated apoptosis in the brain and in behavioral defects. Reduction of atrophin levels in miR-8-expressing cells to below the level generated by miR-8 regulation is detrimental, providing evidence for a "tuning target" relationship between them.? 22 let-7k miRNA apoptosis Danio rerio embryos 22298809 7955 The miRNA expression profiles obtained reveal significant miRNA deregulation and show that both ethanol concentrations upregulate miR-153a, miR-725, miR 30d, let-7k, miR-100, miR-738, and miR-732. Putative gene targets of deregulated miRNAs are involved in cell cycle control, apoptosis, and transcription, which are the main processes affected by ethanol toxicity. 23 miR-100 dre-miR-100 MIMAT0001813 miRNA apoptosis Danio rerio embryos 22298809 7955 The miRNA expression profiles obtained reveal significant miRNA deregulation and show that both ethanol concentrations upregulate miR-153a, miR-725, miR 30d, let-7k, miR-100, miR-738, and miR-732. Putative gene targets of deregulated miRNAs are involved in cell cycle control, apoptosis, and transcription, which are the main processes affected by ethanol toxicity. 24 miR-125b dre-miR-125b-5p,dre-miR-125b-1-5p MIMAT0001821,MIMAT0031963 miRNA tp53 apoptosis down Danio rerio brain 19293287 7955 30590 brp53|drp53|etID22686.5|fb40d06|p53|wu:fb40d06|zgc:111919 ZFIN:ZDB-GENE-990415-270|Ensembl:ENSDARG00000035559|Vega:OTTDARG00000016232 5 - tumor protein p53 protein-coding tumor protein p53 Overexpression of miR-125b represses the endogenous level of p53 protein and suppresses apoptosis in human neuroblastoma cells and human lung fibroblast cells. In contrast, knockdown of miR-125b elevates the level of p53 protein and induces apoptosis in human lung fibroblasts and in the zebrafish brain. 25 miR-153a dre-miR-153a MIMAT0001849 miRNA apoptosis Danio rerio embryos 22298809 7955 The miRNA expression profiles obtained reveal significant miRNA deregulation and show that both ethanol concentrations upregulate miR-153a, miR-725, miR 30d, let-7k, miR-100, miR-738, and miR-732. Putative gene targets of deregulated miRNAs are involved in cell cycle control, apoptosis, and transcription, which are the main processes affected by ethanol toxicity. 26 miR-30a dre-miR-30a-5p,dre-miR-30a-3p MIMAT0001803,MIMAT0031951 miRNA six1a apoptosis down Danio rerio 24634509 7955 494168 six1b|six2|zgc:92332 ZFIN:ZDB-GENE-040718-155|Ensembl:ENSDARG00000039304|Vega:OTTDARG00000022888 13 - SIX homeobox 1a protein-coding SIX homeobox 1a Overexpression of miR30a leads to a reduction in six1a/b levels, and results in increased apoptosis and altered somite morphology, which phenocopies six1a/b knockdown.? 27 miR-30a dre-miR-30a-5p,dre-miR-30a-3p MIMAT0001803,MIMAT0031951 miRNA six1b apoptosis down Danio rerio 24634509 7955 404627 six1|zgc:77345 ZFIN:ZDB-GENE-040426-2308 20 - SIX homeobox 1b protein-coding SIX homeobox 1b Overexpression of miR30a leads to a reduction in six1a/b levels, and results in increased apoptosis and altered somite morphology, which phenocopies six1a/b knockdown.? 28 miR-30d dre-miR-30d MIMAT0001806 miRNA apoptosis Danio rerio embryos 22298809 7955 The miRNA expression profiles obtained reveal significant miRNA deregulation and show that both ethanol concentrations upregulate miR-153a, miR-725, miR 30d, let-7k, miR-100, miR-738, and miR-732. Putative gene targets of deregulated miRNAs are involved in cell cycle control, apoptosis, and transcription, which are the main processes affected by ethanol toxicity. 29 miR-725 dre-miR-725 MIMAT0003753 miRNA apoptosis Danio rerio embryos 22298809 7955 The miRNA expression profiles obtained reveal significant miRNA deregulation and show that both ethanol concentrations upregulate miR-153a, miR-725, miR 30d, let-7k, miR-100, miR-738, and miR-732. Putative gene targets of deregulated miRNAs are involved in cell cycle control, apoptosis, and transcription, which are the main processes affected by ethanol toxicity. 30 miR-732 dre-miR-732 MIMAT0003762 miRNA apoptosis Danio rerio embryos 22298809 7955 The miRNA expression profiles obtained reveal significant miRNA deregulation and show that both ethanol concentrations upregulate miR-153a, miR-725, miR 30d, let-7k, miR-100, miR-738, and miR-732. Putative gene targets of deregulated miRNAs are involved in cell cycle control, apoptosis, and transcription, which are the main processes affected by ethanol toxicity. 31 miR-738 dre-miR-738 MIMAT0003769 miRNA apoptosis Danio rerio embryos 22298809 7955 The miRNA expression profiles obtained reveal significant miRNA deregulation and show that both ethanol concentrations upregulate miR-153a, miR-725, miR 30d, let-7k, miR-100, miR-738, and miR-732. Putative gene targets of deregulated miRNAs are involved in cell cycle control, apoptosis, and transcription, which are the main processes affected by ethanol toxicity. 32 miR-92a dre-miR-92a-2-5p,dre-miR-92a-5p,dre-miR-92a-3p MIMAT0031954,MIMAT0031953,MIMAT0001808 miRNA nog3 apoptosis down Danio rerio Craniofacial cell 23410941 7955 30173 - ZFIN:ZDB-GENE-990714-8|Ensembl:ENSDARG00000079003 12 - noggin 3 protein-coding noggin 3 The Bmp antagonist gene noggin3 (nog3) is a direct target of mir92a. Inactivation of mir92a stabilizes nog3 mRNA, leading to repression of Bmp signaling and abnormal behaviors of chondrogenic progenitors. In contrast, ectopic expression of mir92a duplex decreases nog3 mRNA levels and, as a result, derepresses Bmp signaling and promotes cell apoptosis. 33 miR-125b miRNA itchb apoptosis Danio rerio 21935352 7955 170770 PUMA|PUMA/JFY1 MGI:2181667|Ensembl:ENSMUSG00000002083|Vega:OTTMUSG00000022267 7 7 A2|7 BCL2 binding component 3 protein-coding BCL2 binding component 3 By using a gain- and loss-of-function screen for miR-125b targets in humans, mice, and zebrafish and by validating these targets with the luciferase assay and a novel miRNA pull-down assay, we demonstrate that miR-125b directly represses 20 novel targets in the p53 network.These targets include both apoptosis regulators like Bak1, Igfbp3, Itch, Puma, Prkra, Tp53inp1, Tp53, Zac1 34 miR-125b miRNA tp53inp1 apoptosis Danio rerio 21935352 7955 568021 cb1036|wu:fb70a09|wu:fi13h08|zgc:158431 ZFIN:ZDB-GENE-031018-3|Ensembl:ENSDARG00000028017|Vega:OTTDARG00000027895 16 - tumor protein p53 inducible nuclear protein 1 protein-coding tumor protein p53 inducible nuclear protein 1 By using a gain- and loss-of-function screen for miR-125b targets in humans, mice, and zebrafish and by validating these targets with the luciferase assay and a novel miRNA pull-down assay, we demonstrate that miR-125b directly represses 20 novel targets in the p53 network.These targets include both apoptosis regulators like Bak1, Igfbp3, Itch, Puma, Prkra, Tp53inp1, Tp53, Zac1 35 miR-143 miRNA KLF5 apoptosis Gallus gallus 20064147 9031 418818 - CGNC:12707|Ensembl:ENSGALG00000016927 1 - Kruppel-like factor 5 (intestinal) protein-coding Kruppel-like factor 5 (intestinal) Many of these genes are associated with cell proliferation, apoptosis and tumourigenesis. Six of the up-regulated genes possess at least one potential miR-143 binding site in their 3'UTRs, of these the binding sites of PYCR2, PSTPIP1 and PDCD5 were validated by an in vitro luciferase reporter assay. In addition, several potential targets with important biological functions were identified by the miRanda algorithm and experimentally confirmed. These targets include KLF5, MAP3K7, TARDBP and UBE2E3, which have conserved miR-143 binding sites across multiple vertebrate species. Potential chicken specific miR-143 target sites were also validated for LPIN1, PCK2, PYCR2, METTL14, SLC2A2 and TNFSF10. Overall, the current study suggests that miR-143 is ubiquitously expressed among tissues and is likely to be involved in the regulation of cell proliferation and apoptosis. 36 miR-143 miRNA MAP3K7 apoptosis Gallus gallus 20064147 9031 421808 - CGNC:11625|Ensembl:ENSGALG00000015596 3 - mitogen-activated protein kinase kinase kinase 7 protein-coding mitogen-activated protein kinase kinase kinase 7 Many of these genes are associated with cell proliferation, apoptosis and tumourigenesis. Six of the up-regulated genes possess at least one potential miR-143 binding site in their 3'UTRs, of these the binding sites of PYCR2, PSTPIP1 and PDCD5 were validated by an in vitro luciferase reporter assay. In addition, several potential targets with important biological functions were identified by the miRanda algorithm and experimentally confirmed. These targets include KLF5, MAP3K7, TARDBP and UBE2E3, which have conserved miR-143 binding sites across multiple vertebrate species. Potential chicken specific miR-143 target sites were also validated for LPIN1, PCK2, PYCR2, METTL14, SLC2A2 and TNFSF10. Overall, the current study suggests that miR-143 is ubiquitously expressed among tissues and is likely to be involved in the regulation of cell proliferation and apoptosis. 37 miR-143 miRNA METTL14 apoptosis Gallus gallus 20064147 9031 422684 - CGNC:51803|Ensembl:ENSGALG00000012000 4 - methyltransferase like 14 protein-coding methyltransferase like 14 Many of these genes are associated with cell proliferation, apoptosis and tumourigenesis. Six of the up-regulated genes possess at least one potential miR-143 binding site in their 3'UTRs, of these the binding sites of PYCR2, PSTPIP1 and PDCD5 were validated by an in vitro luciferase reporter assay. In addition, several potential targets with important biological functions were identified by the miRanda algorithm and experimentally confirmed. These targets include KLF5, MAP3K7, TARDBP and UBE2E3, which have conserved miR-143 binding sites across multiple vertebrate species. Potential chicken specific miR-143 target sites were also validated for LPIN1, PCK2, PYCR2, METTL14, SLC2A2 and TNFSF10. Overall, the current study suggests that miR-143 is ubiquitously expressed among tissues and is likely to be involved in the regulation of cell proliferation and apoptosis. 38 miR-143 miRNA PCK2 apoptosis Gallus gallus 20064147 9031 396457 PEPCK-M CGNC:49813 Un - phosphoenolpyruvate carboxykinase 2 (mitochondrial) protein-coding phosphoenolpyruvate carboxykinase 2 (mitochondrial) Many of these genes are associated with cell proliferation, apoptosis and tumourigenesis. Six of the up-regulated genes possess at least one potential miR-143 binding site in their 3'UTRs, of these the binding sites of PYCR2, PSTPIP1 and PDCD5 were validated by an in vitro luciferase reporter assay. In addition, several potential targets with important biological functions were identified by the miRanda algorithm and experimentally confirmed. These targets include KLF5, MAP3K7, TARDBP and UBE2E3, which have conserved miR-143 binding sites across multiple vertebrate species. Potential chicken specific miR-143 target sites were also validated for LPIN1, PCK2, PYCR2, METTL14, SLC2A2 and TNFSF10. Overall, the current study suggests that miR-143 is ubiquitously expressed among tissues and is likely to be involved in the regulation of cell proliferation and apoptosis. 39 miR-143 miRNA PDCD5 apoptosis Gallus gallus 20064147 9031 415765 - CGNC:3442|Ensembl:ENSGALG00000004648 11 - programmed cell death 5 protein-coding programmed cell death 5 Many of these genes are associated with cell proliferation, apoptosis and tumourigenesis. Six of the up-regulated genes possess at least one potential miR-143 binding site in their 3'UTRs, of these the binding sites of PYCR2, PSTPIP1 and PDCD5 were validated by an in vitro luciferase reporter assay. In addition, several potential targets with important biological functions were identified by the miRanda algorithm and experimentally confirmed. These targets include KLF5, MAP3K7, TARDBP and UBE2E3, which have conserved miR-143 binding sites across multiple vertebrate species. Potential chicken specific miR-143 target sites were also validated for LPIN1, PCK2, PYCR2, METTL14, SLC2A2 and TNFSF10. Overall, the current study suggests that miR-143 is ubiquitously expressed among tissues and is likely to be involved in the regulation of cell proliferation and apoptosis. 40 miR-143 miRNA PSTPIP1 apoptosis Gallus gallus 20064147 9031 415349 - CGNC:2009 10 - proline-serine-threonine phosphatase interacting protein 1 protein-coding proline-serine-threonine phosphatase interacting protein 1 Many of these genes are associated with cell proliferation, apoptosis and tumourigenesis. Six of the up-regulated genes possess at least one potential miR-143 binding site in their 3'UTRs, of these the binding sites of PYCR2, PSTPIP1 and PDCD5 were validated by an in vitro luciferase reporter assay. In addition, several potential targets with important biological functions were identified by the miRanda algorithm and experimentally confirmed. These targets include KLF5, MAP3K7, TARDBP and UBE2E3, which have conserved miR-143 binding sites across multiple vertebrate species. Potential chicken specific miR-143 target sites were also validated for LPIN1, PCK2, PYCR2, METTL14, SLC2A2 and TNFSF10. Overall, the current study suggests that miR-143 is ubiquitously expressed among tissues and is likely to be involved in the regulation of cell proliferation and apoptosis. 41 miR-143 miRNA PYCR2 apoptosis Gallus gallus 20064147 9031 769203 - CGNC:55066|Ensembl:ENSGALG00000007300 18 - pyrroline-5-carboxylate reductase family, member 2 protein-coding pyrroline-5-carboxylate reductase family, member 2 Many of these genes are associated with cell proliferation, apoptosis and tumourigenesis. Six of the up-regulated genes possess at least one potential miR-143 binding site in their 3'UTRs, of these the binding sites of PYCR2, PSTPIP1 and PDCD5 were validated by an in vitro luciferase reporter assay. In addition, several potential targets with important biological functions were identified by the miRanda algorithm and experimentally confirmed. These targets include KLF5, MAP3K7, TARDBP and UBE2E3, which have conserved miR-143 binding sites across multiple vertebrate species. Potential chicken specific miR-143 target sites were also validated for LPIN1, PCK2, PYCR2, METTL14, SLC2A2 and TNFSF10. Overall, the current study suggests that miR-143 is ubiquitously expressed among tissues and is likely to be involved in the regulation of cell proliferation and apoptosis. 42 miR-143 miRNA SLC2A2 apoptosis Gallus gallus 20064147 9031 396272 GLUT2 CGNC:49728|Ensembl:ENSGALG00000009306 9 - solute carrier family 2 (facilitated glucose transporter), member 2 protein-coding solute carrier family 2 (facilitated glucose transporter), member 2 Many of these genes are associated with cell proliferation, apoptosis and tumourigenesis. Six of the up-regulated genes possess at least one potential miR-143 binding site in their 3'UTRs, of these the binding sites of PYCR2, PSTPIP1 and PDCD5 were validated by an in vitro luciferase reporter assay. In addition, several potential targets with important biological functions were identified by the miRanda algorithm and experimentally confirmed. These targets include KLF5, MAP3K7, TARDBP and UBE2E3, which have conserved miR-143 binding sites across multiple vertebrate species. Potential chicken specific miR-143 target sites were also validated for LPIN1, PCK2, PYCR2, METTL14, SLC2A2 and TNFSF10. Overall, the current study suggests that miR-143 is ubiquitously expressed among tissues and is likely to be involved in the regulation of cell proliferation and apoptosis. 43 miR-143 miRNA TARDBP apoptosis Gallus gallus 20064147 9031 419453 - CGNC:2099|Ensembl:ENSGALG00000002906 21 - TAR DNA binding protein protein-coding TAR DNA binding protein Many of these genes are associated with cell proliferation, apoptosis and tumourigenesis. Six of the up-regulated genes possess at least one potential miR-143 binding site in their 3'UTRs, of these the binding sites of PYCR2, PSTPIP1 and PDCD5 were validated by an in vitro luciferase reporter assay. In addition, several potential targets with important biological functions were identified by the miRanda algorithm and experimentally confirmed. These targets include KLF5, MAP3K7, TARDBP and UBE2E3, which have conserved miR-143 binding sites across multiple vertebrate species. Potential chicken specific miR-143 target sites were also validated for LPIN1, PCK2, PYCR2, METTL14, SLC2A2 and TNFSF10. Overall, the current study suggests that miR-143 is ubiquitously expressed among tissues and is likely to be involved in the regulation of cell proliferation and apoptosis. 44 miR-143 miRNA TNFSF10 apoptosis Gallus gallus 20064147 9031 378894 TRAIL CGNC:6980|Ensembl:ENSGALG00000009179 9 - tumor necrosis factor (ligand) superfamily, member 10 protein-coding tumor necrosis factor (ligand) superfamily, member 10 Many of these genes are associated with cell proliferation, apoptosis and tumourigenesis. Six of the up-regulated genes possess at least one potential miR-143 binding site in their 3'UTRs, of these the binding sites of PYCR2, PSTPIP1 and PDCD5 were validated by an in vitro luciferase reporter assay. In addition, several potential targets with important biological functions were identified by the miRanda algorithm and experimentally confirmed. These targets include KLF5, MAP3K7, TARDBP and UBE2E3, which have conserved miR-143 binding sites across multiple vertebrate species. Potential chicken specific miR-143 target sites were also validated for LPIN1, PCK2, PYCR2, METTL14, SLC2A2 and TNFSF10. Overall, the current study suggests that miR-143 is ubiquitously expressed among tissues and is likely to be involved in the regulation of cell proliferation and apoptosis. 45 miR-143 miRNA UBE2E3 apoptosis Gallus gallus 20064147 9031 424122 - CGNC:14325|Ensembl:ENSGALG00000020793 7 - ubiquitin-conjugating enzyme E2E 3 protein-coding ubiquitin-conjugating enzyme E2E 3 Many of these genes are associated with cell proliferation, apoptosis and tumourigenesis. Six of the up-regulated genes possess at least one potential miR-143 binding site in their 3'UTRs, of these the binding sites of PYCR2, PSTPIP1 and PDCD5 were validated by an in vitro luciferase reporter assay. In addition, several potential targets with important biological functions were identified by the miRanda algorithm and experimentally confirmed. These targets include KLF5, MAP3K7, TARDBP and UBE2E3, which have conserved miR-143 binding sites across multiple vertebrate species. Potential chicken specific miR-143 target sites were also validated for LPIN1, PCK2, PYCR2, METTL14, SLC2A2 and TNFSF10. Overall, the current study suggests that miR-143 is ubiquitously expressed among tissues and is likely to be involved in the regulation of cell proliferation and apoptosis. 46 miR-15a gga-miR-15a MIMAT0001117 miRNA BCL2 apoptosis down Gallus gallus lung 24887070 9031 396282 bcl-2 CGNC:9759|Ensembl:ENSGALG00000012885 2 - B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 When chicks were incubated in low oxygen (hypoxia), miR-15a was significantly increased in embryonic lung tissue.Bcl-2 was a translationally repressed target of miR-15a in these chickens. 47 miR-21 gga-miR-21-5p,gga-miR-21-3p MIMAT0003774,MIMAT0026643 miRNA PDCD4 apoptosis down Gallus gallus 23055556 9031 374191 - CGNC:6604|Ensembl:ENSGALG00000008700 6 - programmed cell death 4 (neoplastic transformation inhibitor) protein-coding programmed cell death 4 (neoplastic transformation inhibitor) We mapped the gga-miR-21 promoter to the 10th intron of the TMEM49 gene and found it to be driven by AP-1- and Ets-responsive elements. We show here that the viral oncoprotein Meq binds to this promoter, thereby transactivating gga-miR-21 expression. We confirmed that this miRNA targets chicken programmed death cell 4 (PDCD4) and promotes tumor cell growth and apoptosis escape. 48 miR-M3(MDV1) mdv1-miR-M3-5p,mdv1-miR-M3-3p MIMAT0003923,MIMAT0009207 miRNA SMAD2 apoptosis down Gallus gallus T-cell 20962090 9031 395247 MADH2 CGNC:49229|Ensembl:ENSGALG00000014697 Z - SMAD family member 2 protein-coding SMAD family member 2 MDV1-miR-M3 suppressed cisplatin-induced apoptosis by directly downregulating expression at the protein but not the mRNA level of Smad2, a critical component in the transforming growth factor ¦Â signal pathway. 49 BC200 http://lncrna.com/BC200/ lncRNA necrosis Homo sapiens 25645334 9606 TUG1, BC200 and MIR156HG are down regulated when necrosis is induced using a high dose of DOX in both cell lines. 50 HOTAIR http://lncrna.com/hotair/ lncRNA necrosis Homo sapiens sarcoma 23543869 9606 High levels of both MTDH/AEG-1 and HOTAIR in primary sarcoma are correlated with a high probability of metastasis. By contrast, reduced expressio of both MTDH/AEG-1 and HOTAIR is correlated with a good response to treatment in terms of necrosis, 51 TUG1 lncRNA necrosis Homo sapiens 25645334 9606 TUG1, BC200 and MIR155HG are down regulated when necrosis is induced using a high dose of DOX in both cell lines. 52 miR-155 hsa-miR-155-5p,hsa-miR-155-3p MIMAT0000646,MIMAT0004658 miRNA RIPK1 necrosis down Homo sapiens cardiomyocyte progenitor cells 20550618 9606 8737 RIP|RIP1 HGNC:10019|MIM:603453|Ensembl:ENSG00000137275|HPRD:04583|Vega:OTTHUMG00000014134 6 6p25.2 receptor (TNFRSF)-interacting serine-threonine kinase 1 protein-coding receptor (TNFRSF)-interacting serine-threonine kinase 1 RIP-1|cell death protein Microrna-155 prevents necrotic cell death in human cardiomyocyte progenitor cells via targeting RIP1. 53 miR-155hg hsa-miR-155-5p,hsa-miR-155-3p MIMAT0000646,MIMAT0004658 miRNA necrosis Homo sapiens 25645334 9606 TUG1, BC200 and MIR157HG are down regulated when necrosis is induced using a high dose of DOX in both cell lines. 54 miR-24 hsa-miR-24-1-5p,hsa-miR-24-3p,hsa-miR-24-2-5p MIMAT0000079,MIMAT0000080,MIMAT0004497 miRNA BCL2L11 necrosis down Homo sapiens 23098654 9606 10018 BAM|BIM|BOD HGNC:994|MIM:603827|Ensembl:ENSG00000153094|HPRD:04828|Vega:OTTHUMG00000131256 2 2q13 BCL2-like 11 (apoptosis facilitator) protein-coding BCL2-like 11 (apoptosis facilitator) MiR-24 resulted in the largest LDH release, lowest cell viability and highest apoptosis and necrosis rates in normal and ischemic myocytes. Additionally, the mRNA and protein levels of the pro-apoptotic gene, BCL2L11, were down-regulated by miR-24 overexpression and up-regulated by miR-24 deficiency. The luciferase reporter assay confirmed BCL2L11 to be a target of miR-24. 55 miR-874 hsa-miR-874-3p,hsa-miR-874-5p MIMAT0004911,MIMAT0026718 miRNA CASP8 necrosis down Homo sapiens heart 23828572 9606 841 ALPS2B|CAP4|Casp-8|FLICE|MACH|MCH5 HGNC:1509|MIM:601763|Ensembl:ENSG00000064012|HPRD:03459|Vega:OTTHUMG00000132821 2 2q33-q34 caspase 8, apoptosis-related cysteine peptidase protein-coding caspase 8, apoptosis-related cysteine peptidase When suppressed by miR-874, caspase-8 lost the ability to repress necrotic program. In exploring the molecular mechanism by which miR-874 expression is regulated, we identified that Foxo3a could transcriptionally repress miR-874 expression. 56 BANCR http://lncrna.com/bancr/ lncRNA MAP1LC3A autophagy down Homo sapiens papillary thyroid carcinoma 25289082 9606 84557 ATG8E|LC3|LC3A|MAP1ALC3|MAP1BLC3 HGNC:6838|MIM:601242|Ensembl:ENSG00000101460|HPRD:03144|Vega:OTTHUMG00000032306 20 20q11.22 microtubule-associated protein 1 light chain 3 alpha protein-coding microtubule-associated protein 1 light chain 3 alpha In addition,the overexpression of BANCR resulted in an increase in the ratio of LC3-II/LC3-I,a marker for autophagy, while the knockdown of BANCR decreased the ratio of LC3-II/LC3-I. 57 BANCR http://lncrna.com/bancr/ lncRNA MAP1LC3B autophagy up Homo sapiens papillary thyroid carcinoma 25289082 9606 81631 ATG8F|LC3B|MAP1A/1BLC3|MAP1LC3B-a HGNC:13352|MIM:609604|Ensembl:ENSG00000140941|HPRD:14358|Vega:OTTHUMG00000137654 16 16q24.2 microtubule-associated protein 1 light chain 3 beta protein-coding microtubule-associated protein 1 light chain 3 beta In addition,the overexpression of BANCR resulted in an increase in the ratio of LC3-II/LC3-I,a marker for autophagy, while the knockdown of BANCR decreased the ratio of LC3-II/LC3-I. 58 FLJ11812 lncRNA ATG13 autophagy Homo sapiens human umbilical vein endothelial cells 24879147 9606 9776 KIAA0652|PARATARG8 HGNC:29091|MIM:615088|Ensembl:ENSG00000175224|HPRD:13809|Vega:OTTHUMG00000166538 11 11p11.2 autophagy related 13 protein-coding autophagy related 13 In previous studies, we found a chemical small molecule, 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO), that inhibited autophagy in human umbilical vein endothelial cells (HUVECs) and neuronal cells.Finally, we used gene microarray, RNA interference, RNA-ChIP assay, bioinformatics, luciferase reporter assay, and other assays and found that 3BDO greatly decreased the level of a long noncoding RNA (lncRNA) derived from the 3' untranslated region (3'UTR) of TGFB2, known as FLJ11812.Further experiments results showed that FLJ11812 could bind with MIR4459 targeting ATG13 (autophagy-related 13), and ATG13 protein level was decreased along with 3BDO-decreased FLJ11812 level. 59 HULC http://lncrna.com/HULC/ lncRNA autophagy Homo sapiens gastric 24247585 9606 Mechanistically, we discovered that overexpression of HULC could induce patterns of autophagy in SGC7901 cells; more importantly, autophagy inhibition increased overexpression of HULC cell apoptosis. 60 MEG3 http://lncrna.com/MEG3/ lncRNA MAP1LC3B autophagy down Homo sapiens bladder cancer cell lines 23295831 9606 81631 ATG8F|LC3B|MAP1A/1BLC3|MAP1LC3B-a HGNC:13352|MIM:609604|Ensembl:ENSG00000140941|HPRD:14358|Vega:OTTHUMG00000137654 16 16q24.2 microtubule-associated protein 1 light chain 3 beta protein-coding microtubule-associated protein 1 light chain 3 beta A significant negative correlation was observed between MEG3 levels and LC3-II (autophagy marker) levels in vivo. We further demonstrated that MEG3 markedly suppressed autophagy activation, whereas MEG3 knockdown activated autophagy in human bladder cancer cell lines. 61 let-7 hsa-let-7a-5p,hsa-let-7a-3p,hsa-let-7a-2-3p,hsa-let-7b-5p,hsa-let-7b-3p,hsa-let-7c-5p,hsa-let-7c-3p,hsa-let-7d-5p,hsa-let-7d-3p,hsa-let-7e-5p,hsa-let-7e-3p,hsa-let-7g-5p,hsa-let-7g-3p,hsa-let-7i-5p,hsa-let-7i-3p MIMAT0000062,MIMAT0004481,MIMAT0010195,MIMAT0000063,MIMAT0004482,MIMAT0000064,MIMAT0026472,MIMAT0000065,MIMAT0004484,MIMAT0000066,MIMAT0004485,MIMAT0004486,MIMAT0000414,MIMAT0004584,MIMAT0000415,MIMAT0004585 miRNA MTOR autophagy down Homo sapiens brain cell 25295787 9606 2475 FRAP|FRAP1|FRAP2|RAFT1|RAPT1 HGNC:3942|MIM:601231|Ensembl:ENSG00000198793|HPRD:03134|Vega:OTTHUMG00000002001 1 1p36.2 mechanistic target of rapamycin (serine/threonine kinase) protein-coding mechanistic target of rapamycin (serine/threonine kinase) We found that let-7 activates autophagy by coordinately downregulating the amino acid sensing pathway to prevent mTORC1 activation. Let-7 induced autophagy in the brain to eliminate protein aggregates, establishing its physiological relevance for in vivo autophagy modulation. 62 let-7a hsa-let-7a-5p,hsa-let-7a-3p,hsa-let-7a-2-3p MIMAT0000062,MIMAT0004481,MIMAT0010195 miRNA ATG5 autophagy down Homo sapiens HeLa cell 23143396 9606 9474 APG5|APG5-LIKE|APG5L|ASP|hAPG5 HGNC:589|MIM:604261|Ensembl:ENSG00000057663|HPRD:16051|Vega:OTTHUMG00000016193 6 6q21 autophagy related 5 protein-coding autophagy related 5 Levels of miR-16 and let-7a, measured by Northern blot or RT-qPCR, indeed decreased significantly in cells treated with siRNAs targeting NDP52, ATG5 or ATG7, but not p62, for an extended period of 4 days (Fig.4a-b). In contrast, pre-miR-16 and pre-let-7a levels were not overtly modified (Fig.4a-c) suggesting that prolonged defects in autophagy specifically affect miRNA stability after pre-miRNA processing, but before miRISC formation and activity. 63 let-7a hsa-let-7a-5p,hsa-let-7a-3p,hsa-let-7a-2-3p MIMAT0000062,MIMAT0004481,MIMAT0010195 miRNA ATG7 autophagy down Homo sapiens HeLa cell 23143396 9606 10533 APG7-LIKE|APG7L|GSA7 HGNC:16935|MIM:608760|Ensembl:ENSG00000197548|HPRD:12293|Vega:OTTHUMG00000129740 3 3p25.3 autophagy related 7 protein-coding autophagy related 7 Levels of miR-16 and let-7a, measured by Northern blot or RT-qPCR, indeed decreased significantly in cells treated with siRNAs targeting NDP52, ATG5 or ATG7, but not p62, for an extended period of 4 days (Fig.4a-b). In contrast, pre-miR-16 and pre-let-7a levels were not overtly modified (Fig.4a-c) suggesting that prolonged defects in autophagy specifically affect miRNA stability after pre-miRNA processing, but before miRISC formation and activity. 64 let-7a hsa-let-7a-5p,hsa-let-7a-3p,hsa-let-7a-2-3p MIMAT0000062,MIMAT0004481,MIMAT0010195 miRNA CALCOCO2 autophagy down Homo sapiens HeLa cell 23143396 9606 10241 NDP52 HGNC:29912|MIM:604587|Ensembl:ENSG00000136436|HPRD:06846|Vega:OTTHUMG00000160505 17 17q21.32 calcium binding and coiled-coil domain 2 protein-coding calcium binding and coiled-coil domain 2 Levels of miR-16 and let-7a, measured by Northern blot or RT-qPCR, indeed decreased significantly in cells treated with siRNAs targeting NDP52, ATG5 or ATG7, but not p62, for an extended period of 4 days (Fig.4a-b). In contrast, pre-miR-16 and pre-let-7a levels were not overtly modified (Fig.4a-c) suggesting that prolonged defects in autophagy specifically affect miRNA stability after pre-miRNA processing, but before miRISC formation and activity. 65 let-7a hsa-let-7a-5p,hsa-let-7a-3p,hsa-let-7a-2-3p MIMAT0000062,MIMAT0004481,MIMAT0010195 miRNA autophagy Homo sapiens hepatocellular carcinoma 25429777 9606 Chol-let-7a inhibited the viability and mobility of HCC cells. Chol-let-7a was primarily observed in the cytoplasm and induced organelle changes including autophagy. Mild changes were observed in the cells treated with negative control miRNA. 66 let-7f-1 hsa-let-7f-1-3p MIMAT0004486 miRNA HMGB1 autophagy up Homo sapiens medulloblastomacells 25014664 9606 3146 HMG1|HMG3|SBP-1 HGNC:4983|MIM:163905|Ensembl:ENSG00000189403|HPRD:01228|Vega:OTTHUMG00000016670 13 13q12 high mobility group box 1 protein-coding high mobility group box 1 SPARC expression suppressed miR-let-7f-1 expression which resulted in disruptedrepression of High Mobility Group Box 1 (HMGB1), a critical regulator ofautophagy. 67 miR-100 hsa-miR-100-5p,hsa-miR-100-3p MIMAT0000098,MIMAT0004512 miRNA IGF1R autophagy down Homo sapiens HCC cells 25026290 9606 3480 CD221|IGFIR|IGFR|JTK13 HGNC:5465|MIM:147370|Ensembl:ENSG00000140443|HPRD:00932|Vega:OTTHUMG00000149851 15 15q26.3 insulin-like growth factor 1 receptor protein-coding insulin-like growth factor 1 receptor MicroRNA-100 promotes the autophagy of hepatocellular carcinoma cells by inhibiting the expression of mTOR and IGF-1R. 68 miR-100 hsa-miR-100-5p,hsa-miR-100-3p MIMAT0000098,MIMAT0004512 miRNA MTOR autophagy down Homo sapiens HCC cells 25026290 9606 2475 FRAP|FRAP1|FRAP2|RAFT1|RAPT1 HGNC:3942|MIM:601231|Ensembl:ENSG00000198793|HPRD:03134|Vega:OTTHUMG00000002001 1 1p36.2 mechanistic target of rapamycin (serine/threonine kinase) protein-coding mechanistic target of rapamycin (serine/threonine kinase) MicroRNA-100 promotes the autophagy of hepatocellular carcinoma cells by inhibiting the expression of mTOR and IGF-1R. 69 miR-101 hsa-miR-101-5p,hsa-miR-101-3p MIMAT0004513,MIMAT0000099 miRNA ATG4D autophagy Homo sapiens breast cancer cells 21915098 9606 84971 APG4-D|APG4D|AUTL4 HGNC:20789|MIM:611340|Ensembl:ENSG00000130734|HPRD:07005|Vega:OTTHUMG00000180582 19 19p13.2 autophagy related 4D, cysteine peptidase protein-coding autophagy related 4D, cysteine peptidase APG4 autophagy 4 homolog Through transcriptome profiling, we identified three novel miR-101 targets, STMN1, RAB5A and ATG4D. siRNA-mediated depletion of these genes phenocopied the effect of miR-101 overexpression, demonstrating their importance in autophagy regulation. 70 miR-101 hsa-miR-101-5p,hsa-miR-101-3p MIMAT0004513,MIMAT0000099 miRNA ATG4D autophagy down Homo sapiens 22902544 9606 84971 APG4-D|APG4D|AUTL4 HGNC:20789|MIM:611340|Ensembl:ENSG00000130734|HPRD:07005|Vega:OTTHUMG00000180582 19 19p13.2 autophagy related 4D, cysteine peptidase protein-coding autophagy related 4D, cysteine peptidase Several miRNA regulators of this step have been identified including miR-30a, miR-181a and miR-374a (ATG5), miR-630 (ATG12), miR-376b (ATG4), miR-204 (LC3), miR-375 (ATG7), miR-519a (ATG10 and ATG16), miR-885-3p (ATG16) and miR-101 (ATG4 and RAB5A) 71 miR-101 hsa-miR-101-5p,hsa-miR-101-3p MIMAT0004513,MIMAT0000099 miRNA ATG4D autophagy Homo sapiens HepG2 cell line 23483142 9606 84971 APG4-D|APG4D|AUTL4 HGNC:20789|MIM:611340|Ensembl:ENSG00000130734|HPRD:07005|Vega:OTTHUMG00000180582 19 19p13.2 autophagy related 4D, cysteine peptidase protein-coding autophagy related 4D, cysteine peptidase MiR-101 inhibited autophagy via targets including RAB5A, STMN1 and ATG4D. 72 miR-101 hsa-miR-101-5p,hsa-miR-101-3p MIMAT0004513,MIMAT0000099 miRNA RAB5A autophagy Homo sapiens breast cancer cells 21915098 9606 5868 RAB5 HGNC:9783|MIM:179512|Ensembl:ENSG00000144566|HPRD:01542|Vega:OTTHUMG00000129889 3 3p24-p22 RAB5A, member RAS oncogene family protein-coding RAB5A, member RAS oncogene family leukemia-associated phosp Through transcriptome profiling, we identified three novel miR-101 targets, STMN1, RAB5A and ATG4D. siRNA-mediated depletion of these genes phenocopied the effect of miR-101 overexpression, demonstrating their importance in autophagy regulation. 73 miR-101 hsa-miR-101-5p,hsa-miR-101-3p MIMAT0004513,MIMAT0000099 miRNA RAB5A autophagy Homo sapiens HepG2 cell line 23483142 9606 5868 RAB5 HGNC:9783|MIM:179512|Ensembl:ENSG00000144566|HPRD:01542|Vega:OTTHUMG00000129889 3 3p24-p22 RAB5A, member RAS oncogene family protein-coding RAB5A, member RAS oncogene family MiR-101 inhibited autophagy via targets including RAB5A, STMN1 and ATG4D. 74 miR-101 hsa-miR-101-5p,hsa-miR-101-3p MIMAT0004513,MIMAT0000099 miRNA STMN1 autophagy Homo sapiens breast cancer cells 21915098 9606 3925 C1orf215|LAP18|Lag|OP18|PP17|PP19|PR22|SMN HGNC:6510|MIM:151442|Ensembl:ENSG00000117632|HPRD:01047|Vega:OTTHUMG00000007389 1 1p36.11 stathmin 1 protein-coding stathmin 1 leukemia-associated phosp Through transcriptome profiling, we identified three novel miR-101 targets, STMN1, RAB5A and ATG4D. siRNA-mediated depletion of these genes phenocopied the effect of miR-101 overexpression, demonstrating their importance in autophagy regulation. 75 miR-101 hsa-miR-101-5p,hsa-miR-101-3p MIMAT0004513,MIMAT0000099 miRNA STMN1 autophagy Homo sapiens HepG2 cell line 23483142 9606 3925 C1orf215|LAP18|Lag|OP18|PP17|PP19|PR22|SMN HGNC:6510|MIM:151442|Ensembl:ENSG00000117632|HPRD:01047|Vega:OTTHUMG00000007389 1 1p36.11 stathmin 1 protein-coding stathmin 1 MiR-101 inhibited autophagy via targets including RAB5A, STMN1 and ATG4D. 76 miR-101 hsa-miR-101-5p,hsa-miR-101-3p MIMAT0004513,MIMAT0000099 miRNA STMN1 autophagy Homo sapiens NPC cells 25607713 9606 3925 C1orf215|LAP18|Lag|OP18|PP17|PP19|PR22|SMN HGNC:6510|MIM:151442|Ensembl:ENSG00000117632|HPRD:01047|Vega:OTTHUMG00000007389 1 1p36.11 stathmin 1 protein-coding stathmin 1 Stathmin-1(STMN1) was additionally verified as a direct functional target of miR-101, which was found to be involved in cell viability, radioresistance and radiation-induced autophagy of NPC cells. 77 miR-101 hsa-miR-101-5p,hsa-miR-101-3p MIMAT0004513,MIMAT0000099 miRNA autophagy Homo sapiens breast cancer cells 22085996 9606 84971 APG4D|AUTL4|APG4-D HGNC:20789|Ensembl:ENSG00000130734|HPRD:07005|MIM:611340|Vega:OTTHUMG00000180582 19 19p13.2 autophagy related 4D, cysteine peptidase protein coding autophagy related 4D, cysteine peptidase MicroRNA-101 is a potent inhibitor of autophagy. 78 miR-101 hsa-miR-101-5p,hsa-miR-101-3p MIMAT0004513,MIMAT0000099 miRNA autophagy Homo sapiens 22342941 9606 In this review, we focus on highlighting the dual functions of miRNAs as either oncogenes (e.g., miRNA-183, miRNA-376b, miRNA-106a, miRNA-221/222, miRNA-31 and miRNA-34c) or tumor suppressors (e.g., miRNA-30a, miRNA-101 and miRNA-9*) via mediating several autophagic signaling pathways in cancer pathogenesis. Taken together, these findings may uncover the regulatory mechanisms of oncogenic and tumor suppressive miRNAs in autophagy, which would provide a better understanding of miRNA-modulated autophagic signaling networks for future cancer therapeutics. 79 miR-101 hsa-miR-101-5p,hsa-miR-101-3p MIMAT0004513,MIMAT0000099 miRNA autophagy Homo sapiens U-2 OS cells 25013866 9606 While the miR-101 could significantly reduce the doxorubicin-induced AVOs and block the autophagy related protein expression in U-2 OS cells. 80 miR-106a hsa-miR-106a-5p,hsa-miR-106a-3p MIMAT0000103,MIMAT0004517 miRNA ATG12 autophagy down Homo sapiens HCT116 23899543 9606 9140 APG12|APG12L|FBR93|HAPG12 HGNC:588|MIM:609608|Ensembl:ENSG00000145782|HPRD:08496|Vega:OTTHUMG00000128889 5 5q21-q22 autophagy related 12 protein-coding autophagy related 12 MiR-106a and miR-106b overexpression inhibited the expression of several other autophagy genes, including ATG12. 81 miR-106a hsa-miR-106a-5p,hsa-miR-106a-3p MIMAT0000103,MIMAT0004517 miRNA autophagy Homo sapiens 22342941 9606 In this review, we focus on highlighting the dual functions of miRNAs as either oncogenes (e.g., miRNA-183, miRNA-376b, miRNA-106a, miRNA-221/222, miRNA-31 and miRNA-34c) or tumor suppressors (e.g., miRNA-30a, miRNA-101 and miRNA-9*) via mediating several autophagic signaling pathways in cancer pathogenesis. Taken together, these findings may uncover the regulatory mechanisms of oncogenic and tumor suppressive miRNAs in autophagy, which would provide a better understanding of miRNA-modulated autophagic signaling networks for future cancer therapeutics. 82 miR-106b hsa-miR-106b-5p,hsa-miR-106b-3p MIMAT0000680,MIMAT0004672 miRNA ATG12 autophagy down Homo sapiens HCT116 23899543 9606 9140 APG12|APG12L|FBR93|HAPG12 HGNC:588|MIM:609608|Ensembl:ENSG00000145782|HPRD:08496|Vega:OTTHUMG00000128889 5 5q21-q22 autophagy related 12 protein-coding autophagy related 12 MiR-106a and miR-106b overexpression inhibited the expression of several other autophagy genes, including ATG12. 83 miR-106b hsa-miR-106b-5p,hsa-miR-106b-3p MIMAT0000680,MIMAT0004672 miRNA ATG16L1 autophagy down Homo sapiens HCT116 23899543 9606 55054 APG16L|ATG16A|ATG16L|IBD10|WDR30 HGNC:21498|MIM:610767|Ensembl:ENSG00000085978|HPRD:16498|Vega:OTTHUMG00000133619 2 2q37.1 autophagy related 16-like 1 (S. cerevisiae) protein-coding autophagy related 16-like 1 (S. cerevisiae) Both miR-106a and miR-106b mimics inhibited starvation-induced autophagy. The miR-106b mimic reduced ATG16L1 protein expression. 84 miR-106b hsa-miR-106b-5p,hsa-miR-106b-3p MIMAT0000680,MIMAT0004672 miRNA ATG16L1 autophagy down Homo sapiens 24036151 9606 55054 APG16L|ATG16A|ATG16L|IBD10|WDR30 HGNC:21498|MIM:610767|Ensembl:ENSG00000085978|HPRD:16498|Vega:OTTHUMG00000133619 2 2q37.1 autophagy related 16-like 1 (S. cerevisiae) protein-coding autophagy related 16-like 1 (S. cerevisiae) Silencing Dicer1, an essential processor of miRs, increased levels of ATG protein and formation of autophagosomes in cells, indicating that miRs regulate autophagy. Luciferase reporter assays indicated that MIR106B and MIR93 targeted ATG16L1 messenger RNA. MIR106B and MIR93 reduced levels of ATG16L1 and autophagy; t 85 miR-106b hsa-miR-106b-5p,hsa-miR-106b-3p MIMAT0000680,MIMAT0004672 miRNA SQSTM1 autophagy up Homo sapiens myeloid 32D cells 22441107 9606 8878 A170|OSIL|PDB3|ZIP3|p60|p62|p62B HGNC:11280|MIM:601530|Ensembl:ENSG00000161011|HPRD:03319|Vega:OTTHUMG00000150643 5 5q35 sequestosome 1 protein-coding sequestosome 1 SQSTM1 (sequestosome 1/p62), a multiple domain protein that acts as a signaling hub, was identified as a key target for these miRNAs. SQSTM1 can interfere with autophagy via binding to the autophagic regulator Atg8/LC3. 86 miR-106b hsa-miR-106b-5p,hsa-miR-106b-3p MIMAT0000680,MIMAT0004672 miRNA ULK1 autophagy down Homo sapiens myoblast cell line cells 22781751 9606 8408 ATG1|ATG1A|UNC51|Unc51.1|hATG1 HGNC:12558|MIM:603168|Ensembl:ENSG00000177169|HPRD:11933|Vega:OTTHUMG00000168052 12 12q24.3 unc-51 like autophagy activating kinase 1 protein-coding unc-51 like autophagy activating kinase 1 MiR-20a and miR-106b negatively regulate autophagy induced by leucine deprivation via suppression of ULK1 expression in C2C12 myoblasts. 87 miR-124 hsa-miR-124-3p,hsa-miR-124-5p MIMAT0000422,MIMAT0004591 miRNA ANTXR2 autophagy down Homo sapiens Jurkat cells 25736362 9606 118429 CMG-2|CMG2|HFS|ISH|JHF HGNC:21732|MIM:608041|Ensembl:ENSG00000163297|HPRD:07452|Vega:OTTHUMG00000151982 4 4q21.21 anthrax toxin receptor 2 protein-coding anthrax toxin receptor 2 ANTXR2 inhibition by miR-124 promoted JNK activation and induced autophagy. 88 miR-124 hsa-miR-124-3p,hsa-miR-124-5p MIMAT0000422,MIMAT0004591 miRNA autophagy Homo sapiens 21293178 9606 MicroRNA enrichment analysis revealed miR-130, 98, 124, 204 and 142 as the putative post-transcriptional regulators of the autophagy-lysosomal pathway genes. 89 miR-130 hsa-miR-96-5p,hsa-miR-96-3p MIMAT0000095,MIMAT0004510 miRNA autophagy Homo sapiens 21293178 9606 MicroRNA enrichment analysis revealed miR-130, 98, 124, 204 and 142 as the putative post-transcriptional regulators of the autophagy-lysosomal pathway genes. 90 miR-130a hsa-miR-130a-3p,hsa-miR-130a-5p MIMAT0000425 ,MIMAT0004593 miRNA ATG16L1 autophagy down Homo sapiens ileal biopsy 24148619 9606 55054 APG16L|ATG16A|ATG16L|IBD10|WDR30 HGNC:21498|MIM:610767|Ensembl:ENSG00000085978|HPRD:16498|Vega:OTTHUMG00000133619 2 2q37.1 autophagy related 16-like 1 (S. cerevisiae) protein-coding autophagy related 16-like 1 (S. cerevisiae) In ileal biopsy samples of patients with CD, there was an inverse correlation between levels of MIR30C and MIR130A and those of ATG5 and ATG16L1, supporting in vitro findings. Inhibition of MIR30C and MIR130A in cultured intestinal epithelial cells and in mouse enterocytes blocked AIEC-induced inhibition of ATG5 and ATG16L1 expression and restored functional autophagy. 91 miR-130a hsa-miR-130a-3p,hsa-miR-130a-5p MIMAT0000425 ,MIMAT0004593 miRNA ATG2B autophagy down Homo sapiens chronic lymphocytic leukemia cell 22350415 9606 55102 C14orf103 HGNC:20187|Ensembl:ENSG00000066739|HPRD:12626|Vega:OTTHUMG00000149933 14 14q32.2 autophagy related 2B protein-coding autophagy related 2B Notably, miR-130a inhibited autophagy by reducing autophagosome formation, an effect mediated by downregulation of the genes ATG2B and DICER1, the latter of which is a major component of the miRNA silencing machinery. 92 miR-130a hsa-miR-130a-3p,hsa-miR-130a-5p MIMAT0000425,MIMAT0004593 miRNA ATG2B autophagy down Homo sapiens 22902544 9606 55102 C14orf103 HGNC:20187|Ensembl:ENSG00000066739|HPRD:12626|Vega:OTTHUMG00000149933 14 14q32.2 autophagy related 2B protein-coding autophagy related 2B Retrieval is a poorly defined event in mammalian cells in which the ATG9-ATG2-ATG18 complex participates and probably recruits lipids and other regulatory proteins to the growing phagophore. miRNAs identified to regulate this step include miR-34a (ATG9) and miR-130a (ATG2) 93 miR-130a hsa-miR-130a-3p,hsa-miR-130a-5p MIMAT0000425 ,MIMAT0004593 miRNA ATG5 autophagy down Homo sapiens ileal biopsy 24148619 9606 9474 APG5|APG5-LIKE|APG5L|ASP|hAPG5 HGNC:589|MIM:604261|Ensembl:ENSG00000057663|HPRD:16051|Vega:OTTHUMG00000016193 6 6q21 autophagy related 5 protein-coding autophagy related 5 In ileal biopsy samples of patients with CD, there was an inverse correlation between levels of MIR30C and MIR130A and those of ATG5 and ATG16L1, supporting in vitro findings. Inhibition of MIR30C and MIR130A in cultured intestinal epithelial cells and in mouse enterocytes blocked AIEC-induced inhibition of ATG5 and ATG16L1 expression and restored functional autophagy. 94 miR-130a hsa-miR-130a-3p,hsa-miR-130a-5p MIMAT0000425 ,MIMAT0004593 miRNA BCL2 autophagy Homo sapiens EPC 24750349 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 In conclusion, miR-130a is important for maintaining normal autophagy levels and promoting the survival of EPC via regulation of Bcl-2 and Beclin1 expression, via Runx3. MiR-130a may be a regulator linking apoptosis and the autophagy of EPC 95 miR-130a hsa-miR-130a-3p,hsa-miR-130a-5p MIMAT0000425 ,MIMAT0004593 miRNA BECN1 autophagy Homo sapiens endothelial progenitor cell 24750349 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related In conclusion, miR-130a is important for maintaining normal autophagy levels and promoting the survival of EPC via regulation of Bcl-2 and Beclin1 expression, via Runx3. MiR-130a may be a regulator linking apoptosis and the autophagy of EPC 96 miR-130a hsa-miR-130a-3p,hsa-miR-130a-5p MIMAT0000425 ,MIMAT0004593 miRNA DICER1 autophagy down Homo sapiens chronic lymphocytic leukemia cell 22350415 9606 23405 DCR1|Dicer|HERNA|MNG1|RMSE2 HGNC:17098|MIM:606241|Ensembl:ENSG00000100697|HPRD:05875|Vega:OTTHUMG00000166134 14 14q32.13 dicer 1, ribonuclease type III protein-coding dicer 1, ribonuclease type III Notably, miR-130a inhibited autophagy by reducing autophagosome formation, an effect mediated by downregulation of the genes ATG2B and DICER1, the latter of which is a major component of the miRNA silencing machinery. 97 miR-130a hsa-miR-130a-3p,hsa-miR-130a-5p MIMAT0000425 ,MIMAT0004593 miRNA RUNX3 autophagy Homo sapiens endothelial progenitor cell 24750349 9606 864 AML2|CBFA3|PEBP2aC HGNC:10473|MIM:600210|Ensembl:ENSG00000020633|HPRD:02565|Vega:OTTHUMG00000003316 1 1p36 runt-related transcription factor 3 protein-coding runt-related transcription factor 3 In conclusion, miR-130a is important for maintaining normal autophagy levels and promoting the survival of EPC via regulation of Bcl-2 and Beclin1 expression, via Runx3. MiR-130a may be a regulator linking apoptosis and the autophagy of EPC 98 miR-137 hsa-miR-137 MIMAT0000429 miRNA BNIP3L autophagy down Homo sapiens 24573672 9606 665 BNIP3a|NIX HGNC:1085|MIM:605368|Ensembl:ENSG00000104765|HPRD:07288|Vega:OTTHUMG00000099433 8 8p21 BCL2/adenovirus E1B 19kDa interacting protein 3-like protein-coding BCL2/adenovirus E1B 19kDa interacting protein 3-like Impaired mitophagy in response to hypoxia caused by miR-137 is reversed by re-expression of FUNDC1 and NIX expression vectors lacking the miR-137 recognition sites at their 3' UTR. 99 miR-142 hsa-miR-142-5p,hsa-miR-142-3p MIMAT0000433,MIMAT0000434 miRNA autophagy Homo sapiens 21293178 9606 MicroRNA enrichment analysis revealed miR-130, 98, 124, 204 and 142 as the putative post-transcriptional regulators of the autophagy-lysosomal pathway genes. 100 miR-142-3p hsa-miR-142-3p MIMAT0000434 miRNA ATG16L1 autophagy down Homo sapiens epithelial cell|Jurkat T cell. 24401604 9606 55054 APG16L|ATG16A|ATG16L|IBD10|WDR30 HGNC:21498|MIM:610767|Ensembl:ENSG00000085978|HPRD:16498|Vega:OTTHUMG00000133619 2 2q37.1 autophagy related 16-like 1 (S. cerevisiae) protein-coding autophagy related 16-like 1 (S. cerevisiae) We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 101 miR-143 hsa-miR-143-3p,hsa-miR-143-5p MIMAT0000435,MIMAT0004599 miRNA ATG2B autophagy down Homo sapiens NSCLC H1299 cells 25322940 9606 55102 C14orf103 HGNC:20187|Ensembl:ENSG00000066739|HPRD:12626|Vega:OTTHUMG00000149933 14 14q32.2 autophagy related 2B protein-coding autophagy related 2B In the present study, the autophagy gene, autophagy-related 2B (ATG2B), was identified as a novel target of miR-143. The overexpression of miR-143 was able to downregulate the expression of atg2b at the transcriptional and translational levels by direct binding to its 3' untranslated region. 102 miR-143 hsa-miR-143-3p,hsa-miR-143-5p MIMAT0000435,MIMAT0004599 miRNA autophagy Homo sapiens osteosarcoma tumor cells 25576341 9606 The chemoresistance of osteosarcoma tumor cells to doxorubicin is associated with the downregulation of miR-143 expression, activation of ALDH1+CD133+ cells, activation of autophagy, and inhibition of cell death. 103 miR-144 hsa-miR-144-3p,hsa-miR-144-5p MIMAT0000436,MIMAT0004600 miRNA AKT1 autophagy up Homo sapiens heart 25060662 9606 207 AKT|CWS6|PKB|PKB-ALPHA|PRKBA|RAC|RAC-ALPHA HGNC:391|MIM:164730|Ensembl:ENSG00000142208|HPRD:01261|Vega:OTTHUMG00000170795 14 14q32.32 v-akt murine thymoma viral oncogene homolog 1 protein-coding v-akt murine thymoma viral oncogene homolog 1 Going along with this systemic treatment with miR-144 increased P-Akt, P-GSK3¦Â and P-p44/42 MAPK, decreased p-mTOR level and induced autophagy signaling, and induced early and delayed cardioprotection with improved functional recovery and reduction in infarct size similar to that achieved by rIPC. 104 miR-144 hsa-miR-144-3p,hsa-miR-144-5p MIMAT0000436,MIMAT0004600 miRNA ATG4A autophagy down Homo sapiens RAW264.7 cells 25652854 9606 115201 APG4A|AUTL2 HGNC:16489|MIM:300663|Ensembl:ENSG00000101844|HPRD:06455|Vega:OTTHUMG00000022176 X Xq22.1-q22.3 autophagy related 4A, cysteine peptidase protein-coding autophagy related 4A, cysteine peptidase Conclusion miR-144 can directly inhibit the autophagy-related gene Atg4a expression and participate in the regulation of autophagy process in Mycobacterium tuberculosis infection 105 miR-144 hsa-miR-144-3p,hsa-miR-144-5p MIMAT0000436,MIMAT0004600 miRNA C12orf5 autophagy Homo sapiens lung cancer cell 25660220 9606 57103 FR2BP|TIGAR HGNC:1185|MIM:610775|HPRD:12610 12 12p13.3 chromosome 12 open reading frame 5 protein-coding chromosome 12 open reading frame 5 MiR-144 Inhibits Proliferation and Induces Apoptosis and Autophagy in Lung Cancer Cells by Targeting TIGAR. 106 miR-144 hsa-miR-144-3p,hsa-miR-144-5p MIMAT0000436,MIMAT0004600 miRNA GSK3B autophagy up Homo sapiens heart 25060662 9606 2932 - HGNC:4617|MIM:605004|Ensembl:ENSG00000082701|HPRD:05418|Vega:OTTHUMG00000133765 3 3q13.3 glycogen synthase kinase 3 beta protein-coding glycogen synthase kinase 3 beta Going along with this systemic treatment with miR-144 increased P-Akt, P-GSK3¦Â and P-p44/42 MAPK, decreased p-mTOR level and induced autophagy signaling, and induced early and delayed cardioprotection with improved functional recovery and reduction in infarct size similar to that achieved by rIPC. 107 miR-144 hsa-miR-144-3p,hsa-miR-144-5p MIMAT0000436,MIMAT0004600 miRNA MAPK1 autophagy up Homo sapiens heart 25060662 9606 5594 ERK|ERK-2|ERK2|ERT1|MAPK2|P42MAPK|PRKM1|PRKM2|p38|p40|p41|p41mapk|p42-MAPK HGNC:6871|MIM:176948|Ensembl:ENSG00000100030|HPRD:01496|Vega:OTTHUMG00000030508 22 22q11.21 mitogen-activated protein kinase 1 protein-coding mitogen-activated protein kinase 1 Going along with this systemic treatment with miR-144 increased P-Akt, P-GSK3¦Â and P-p44/42 MAPK, decreased p-mTOR level and induced autophagy signaling, and induced early and delayed cardioprotection with improved functional recovery and reduction in infarct size similar to that achieved by rIPC. 108 miR-144 hsa-miR-144-3p,hsa-miR-144-5p MIMAT0000436,MIMAT0004600 miRNA MAPK3 autophagy up Homo sapiens heart 25060662 9606 5595 ERK-1|ERK1|ERT2|HS44KDAP|HUMKER1A|P44ERK1|P44MAPK|PRKM3|p44-ERK1|p44-MAPK HGNC:6877|MIM:601795|Ensembl:ENSG00000102882|HPRD:03479|Vega:OTTHUMG00000132149 16 16p11.2 mitogen-activated protein kinase 3 protein-coding mitogen-activated protein kinase 3 Going along with this systemic treatment with miR-144 increased P-Akt, P-GSK3¦Â and P-p44/42 MAPK, decreased p-mTOR level and induced autophagy signaling, and induced early and delayed cardioprotection with improved functional recovery and reduction in infarct size similar to that achieved by rIPC. 109 miR-144 hsa-miR-144-3p,hsa-miR-144-5p MIMAT0000436,MIMAT0004600 miRNA MTOR autophagy down Homo sapiens heart 25060662 9606 2475 FRAP|FRAP1|FRAP2|RAFT1|RAPT1 HGNC:3942|MIM:601231|Ensembl:ENSG00000198793|HPRD:03134|Vega:OTTHUMG00000002001 1 1p36.2 mechanistic target of rapamycin (serine/threonine kinase) protein-coding mechanistic target of rapamycin (serine/threonine kinase) Going along with this systemic treatment with miR-144 increased P-Akt, P-GSK3¦Â and P-p44/42 MAPK, decreased p-mTOR level and induced autophagy signaling, and induced early and delayed cardioprotection with improved functional recovery and reduction in infarct size similar to that achieved by rIPC. 110 miR-152 hsa-miR-152-3p,hsa-miR-152-5p MIMAT0000438,MIMAT0026479 miRNA ATG14 autophagy down Homo sapiens ovarian cancer cell 25650716 9606 22863 ATG14L|BARKOR|KIAA0831 HGNC:19962|MIM:613515|Ensembl:ENSG00000126775|HPRD:13820|Vega:OTTHUMG00000172129 14 14q22.3 autophagy related 14 protein-coding autophagy related 14 Downregulation of ATG14 by EGR1-MIR152 sensitizes ovarian cancer cells to cisplatin-induced apoptosis by inhibiting cyto-protective autophagy. 111 miR-152 hsa-miR-152-3p,hsa-miR-152-5p MIMAT0000438,MIMAT0026479 miRNA COPZ2 autophagy Homo sapiens 21746916 9606 51226 zeta2-COP HGNC:19356|MIM:615526|Ensembl:ENSG00000005243|HPRD:16739 17 17q21.32 coatomer protein complex, subunit zeta 2 protein-coding coatomer protein complex, subunit zeta 2 COPZ2 displays no tumor-suppressive activities, but it harbors microRNA 152, which is silenced in tumor cells concurrently with COPZ2 and acts as a tumor suppressor in vitro and in vivo. 112 miR-155 hsa-miR-155-5p,hsa-miR-155-3p MIMAT0000646,MIMAT0004658 miRNA ATG7 autophagy down Homo sapiens 24130493 9606 10533 APG7-LIKE|APG7L|GSA7 HGNC:16935|MIM:608760|Ensembl:ENSG00000197548|HPRD:12293|Vega:OTTHUMG00000129740 3 3p25.3 autophagy related 7 protein-coding autophagy related 7 Furthermore, blocking autophagy with specific inhibitor 3-methyladenine or silencing of autophagy related gene 7 (Atg7) reduced the ability of miR-155 to promote autophagy and mycobacterial elimination. More importantly, our study demonstrated that miR-155 bound to the 3'-untranslated region of Ras homologue enriched in brain (Rheb), a negative regulator of autophagy, accelerated the process of autophagy and sequential killing of intracellular mycobacteria by suppressing Rheb expression. 113 miR-155 hsa-miR-155-5p,hsa-miR-155-3p MIMAT0000646,MIMAT0004658 miRNA GSK3B autophagy down Homo sapiens 24343269 9606 2932 - HGNC:4617|MIM:605004|Ensembl:ENSG00000082701|HPRD:05418|Vega:OTTHUMG00000133765 3 3q13.3 glycogen synthase kinase 3 beta protein-coding glycogen synthase kinase 3 beta Importantly, cellular levels of PP2A, a phosphatase, were regulated by Mir155 and Mir31 to fine-tune autophagy. Diminished expression of PP2A led to inhibition of GSK3B, thus facilitating the prolonged activation of WNT and SHH signaling pathways. Sustained WNT and SHH signaling effectuated the expression of anti-inflammatory lipoxygenases, which in tandem inhibited IFNG-induced JAK-STAT signaling and contributed to evasion of autophagy. 114 miR-155 hsa-miR-155-5p,hsa-miR-155-3p MIMAT0000646,MIMAT0004658 miRNA PPP2R4 autophagy down Homo sapiens 24343269 9606 5524 PP2A|PR53|PTPA HGNC:9308|MIM:600756|Ensembl:ENSG00000119383|HPRD:02858|Vega:OTTHUMG00000020774 9 9q34 protein phosphatase 2A activator, regulatory subunit 4 protein-coding protein phosphatase 2A activator, regulatory subunit 4 Importantly, cellular levels of PP2A, a phosphatase, were regulated by Mir155 and Mir31 to fine-tune autophagy. Diminished expression of PP2A led to inhibition of GSK3B, thus facilitating the prolonged activation of WNT and SHH signaling pathways. Sustained WNT and SHH signaling effectuated the expression of anti-inflammatory lipoxygenases, which in tandem inhibited IFNG-induced JAK-STAT signaling and contributed to evasion of autophagy. 115 miR-155 hsa-miR-155-5p,hsa-miR-155-3p MIMAT0000646,MIMAT0004658 miRNA RHEB autophagy down Homo sapiens brain 24130493 9606 6009 RHEB2 HGNC:10011|MIM:601293|Ensembl:ENSG00000106615|HPRD:03188|Vega:OTTHUMG00000157330 7 7q36 Ras homolog enriched in brain protein-coding Ras homolog enriched in brain Furthermore, blocking autophagy with specific inhibitor 3-methyladenine or silencing of autophagy related gene 7 (Atg7) reduced the ability of miR-155 to promote autophagy and mycobacterial elimination. More importantly, our study demonstrated that miR-155 bound to the 3'-untranslated region of Ras homologue enriched in brain (Rheb), a negative regulator of autophagy, accelerated the process of autophagy and sequential killing of intracellular mycobacteria by suppressing Rheb expression. 116 miR-155 hsa-miR-155-5p,hsa-miR-155-3p MIMAT0000646,MIMAT0000646 miRNA RHEB autophagy down Homo sapiens asopharyngeal cancer and cervical cancer cell 24262949 9606 6009 RHEB2 HGNC:10011|MIM:601293|Ensembl:ENSG00000106615|HPRD:03188|Vega:OTTHUMG00000157330 7 7q36 Ras homolog enriched in brain protein-coding Ras homolog enriched in brain Enforced expression of MIR155 increases autophagic activity in human nasopharyngeal cancer and cervical cancer cells. Knocking down endogenous MIR155 inhibits hypoxia-induced autophagy. We demonstrated that MIR155 targets multiple players in MTOR signaling, including RHEB, RICTOR, and RPS6KB2. MIR155 suppresses target-gene expression by directly interacting with their 3' untranslated regions (UTRs), mutations of the binding sites abolish their MIR155 responsiveness. 117 miR-155 hsa-miR-155-5p,hsa-miR-155-3p MIMAT0004658,MIMAT0000646 miRNA RICTOR autophagy down Homo sapiens asopharyngeal cancer and cervical cancer cell 24262949 9606 253260 AVO3|PIA|hAVO3 HGNC:28611|MIM:609022|Ensembl:ENSG00000164327|HPRD:10682|Vega:OTTHUMG00000162037 5 5p13.1 RPTOR independent companion of MTOR, complex 2 protein-coding RPTOR independent companion of MTOR, complex 2 Enforced expression of MIR155 increases autophagic activity in human nasopharyngeal cancer and cervical cancer cells. Knocking down endogenous MIR155 inhibits hypoxia-induced autophagy. We demonstrated that MIR155 targets multiple players in MTOR signaling, including RHEB, RICTOR, and RPS6KB2. MIR155 suppresses target-gene expression by directly interacting with their 3' untranslated regions (UTRs), mutations of the binding sites abolish their MIR155 responsiveness. 118 miR-155 hsa-miR-155-5p,hsa-miR-155-3p MIMAT0000646,MIMAT0000646 miRNA RPS6KB2 autophagy down Homo sapiens asopharyngeal cancer and cervical cancer cell 24262949 9606 6199 KLS|P70-beta|P70-beta-1|P70-beta-2|S6K-beta2|S6K2|SRK|STK14B|p70(S6K)-beta|p70S6Kb HGNC:10437|MIM:608939|Ensembl:ENSG00000175634|HPRD:10203|Vega:OTTHUMG00000167673 11 11q13.2 ribosomal protein S6 kinase, 70kDa, polypeptide 2 protein-coding ribosomal protein S6 kinase, 70kDa, polypeptide 2 Enforced expression of MIR155 increases autophagic activity in human nasopharyngeal cancer and cervical cancer cells. Knocking down endogenous MIR155 inhibits hypoxia-induced autophagy. We demonstrated that MIR155 targets multiple players in MTOR signaling, including RHEB, RICTOR, and RPS6KB2. MIR155 suppresses target-gene expression by directly interacting with their 3' untranslated regions (UTRs), mutations of the binding sites abolish their MIR155 responsiveness. 119 miR-16 hsa-miR-16-5p,hsa-miR-16-1-3p,hsa-miR-16-2-3p MIMAT0000069,MIMAT0004489,MIMAT0004518 miRNA ATG5 autophagy down Homo sapiens HeLa cell 23143396 9606 9474 APG5|APG5-LIKE|APG5L|ASP|hAPG5 HGNC:589|MIM:604261|Ensembl:ENSG00000057663|HPRD:16051|Vega:OTTHUMG00000016193 6 6q21 autophagy related 5 protein-coding autophagy related 5 Levels of miR-16 and let-7a, measured by Northern blot or RT-qPCR, indeed decreased significantly in cells treated with siRNAs targeting NDP52, ATG5 or ATG7, but not p62, for an extended period of 4 days (Fig.4a-b). In contrast, pre-miR-16 and pre-let-7a levels were not overtly modified (Fig.4a-c) suggesting that prolonged defects in autophagy specifically affect miRNA stability after pre-miRNA processing, but before miRISC formation and activity. 120 miR-16 hsa-miR-16-5p,hsa-miR-16-1-3p,hsa-miR-16-2-3p MIMAT0000069,MIMAT0004489,MIMAT0004518 miRNA ATG7 autophagy down Homo sapiens HeLa cell 23143396 9606 10533 APG7-LIKE|APG7L|GSA7 HGNC:16935|MIM:608760|Ensembl:ENSG00000197548|HPRD:12293|Vega:OTTHUMG00000129740 3 3p25.3 autophagy related 7 protein-coding autophagy related 7 Levels of miR-16 and let-7a, measured by Northern blot or RT-qPCR, indeed decreased significantly in cells treated with siRNAs targeting NDP52, ATG5 or ATG7, but not p62, for an extended period of 4 days (Fig.4a-b). In contrast, pre-miR-16 and pre-let-7a levels were not overtly modified (Fig.4a-c) suggesting that prolonged defects in autophagy specifically affect miRNA stability after pre-miRNA processing, but before miRISC formation and activity. 121 miR-16 hsa-miR-16-5p,hsa-miR-16-1-3p,hsa-miR-16-2-3p MIMAT0000069,MIMAT0004489,MIMAT0004518 miRNA CALCOCO2 autophagy down Homo sapiens HeLa cell 23143396 9606 10241 NDP52 HGNC:29912|MIM:604587|Ensembl:ENSG00000136436|HPRD:06846|Vega:OTTHUMG00000160505 17 17q21.32 calcium binding and coiled-coil domain 2 protein-coding calcium binding and coiled-coil domain 2 Levels of miR-16 and let-7a, measured by Northern blot or RT-qPCR, indeed decreased significantly in cells treated with siRNAs targeting NDP52, ATG5 or ATG7, but not p62, for an extended period of 4 days (Fig.4a-b). In contrast, pre-miR-16 and pre-let-7a levels were not overtly modified (Fig.4a-c) suggesting that prolonged defects in autophagy specifically affect miRNA stability after pre-miRNA processing, but before miRISC formation and activity. 122 miR-17 hsa-miR-17-5p,hsa-miR-17-3p MIMAT0000070,MIMAT0000071 miRNA ATG7 autophagy down Homo sapiens glioblastoma cells 23792642 9606 10533 APG7-LIKE|APG7L|GSA7 HGNC:16935|MIM:608760|Ensembl:ENSG00000197548|HPRD:12293|Vega:OTTHUMG00000129740 3 3p25.3 autophagy related 7 protein-coding autophagy related 7 We demonstrated that ATG7 is a potential target for miR-17, and this miRNA could negatively regulate ATG7 expression, resulting in a modulation of the autophagic status in T98G glioblastoma cells. 123 miR-17 hsa-miR-17-5p,hsa-miR-17-3p MIMAT0000070,MIMAT0000071 miRNA ATG7 autophagy down Homo sapiens hepatocellular carcinoma 25617127 9606 10533 APG7-LIKE|APG7L|GSA7 HGNC:16935|MIM:608760|Ensembl:ENSG00000197548|HPRD:12293|Vega:OTTHUMG00000129740 3 3p25.3 autophagy related 7 protein-coding autophagy related 7 The overexpressed PTENP1 decoyed oncomirs miR-17, miR-19b and miR-20a, which would otherwise target PTEN, PHLPP (a negative AKT regulator) and such autophagy genes as ULK1, ATG7 and p62, indicating that PTENP1 modulated the HCC cell behavior and gene networks by miRNA regulation. 124 miR-17 hsa-miR-17-5p,hsa-miR-17-3p MIMAT0000070,MIMAT0000071 miRNA SQSTM1 autophagy up Homo sapiens myeloid 32D cells 22441107 9606 8878 A170|OSIL|PDB3|ZIP3|p60|p62|p62B HGNC:11280|MIM:601530|Ensembl:ENSG00000161011|HPRD:03319|Vega:OTTHUMG00000150643 5 5q35 sequestosome 1 protein-coding sequestosome 1 SQSTM1 (sequestosome 1/p62), a multiple domain protein that acts as a signaling hub, was identified as a key target for these miRNAs. SQSTM1 can interfere with autophagy via binding to the autophagic regulator Atg8/LC3. 125 miR-17 hsa-miR-17-5p,hsa-miR-17-3p MIMAT0000070,MIMAT0000071 miRNA SQSTM1 autophagy down Homo sapiens hepatocellular carcinoma 25617127 9606 8878 A170|OSIL|PDB3|ZIP3|p60|p62|p62B HGNC:11280|MIM:601530|Ensembl:ENSG00000161011|HPRD:03319|Vega:OTTHUMG00000150643 5 5q35 sequestosome 1 protein-coding sequestosome 1 The overexpressed PTENP1 decoyed oncomirs miR-17, miR-19b and miR-20a, which would otherwise target PTEN, PHLPP (a negative AKT regulator) and such autophagy genes as ULK1, ATG7 and p62, indicating that PTENP1 modulated the HCC cell behavior and gene networks by miRNA regulation. 126 miR-17 hsa-miR-17-5p,hsa-miR-17-3p MIMAT0000070,MIMAT0000071 miRNA ULK1 autophagy down Homo sapiens hepatocellular carcinoma 25617127 9606 8408 ATG1|ATG1A|UNC51|Unc51.1|hATG1 HGNC:12558|MIM:603168|Ensembl:ENSG00000177169|HPRD:11933|Vega:OTTHUMG00000168052 12 12q24.3 unc-51 like autophagy activating kinase 1 protein-coding unc-51 like autophagy activating kinase 1 The overexpressed PTENP1 decoyed oncomirs miR-17, miR-19b and miR-20a, which would otherwise target PTEN, PHLPP (a negative AKT regulator) and such autophagy genes as ULK1, ATG7 and p62, indicating that PTENP1 modulated the HCC cell behavior and gene networks by miRNA regulation. 127 miR-181a hsa-miR-181a-5p,hsa-miR-181a-3p,hsa-miR-181a-2-3p MIMAT0000256,MIMAT0000270,MIMAT0004558 miRNA ATG10 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 83734 APG10|APG10L|pp12616 HGNC:20315|MIM:610800|Ensembl:ENSG00000152348|HPRD:16497|Vega:OTTHUMG00000119041 5 5q14.1 autophagy related 10 protein-coding autophagy related 10 We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 128 miR-181a hsa-miR-181a-5p,hsa-miR-181a-2-3p,hsa-miR-181a-3p MIMAT0000270,MIMAT0004558,MIMAT0000256 miRNA ATG12 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 9140 APG12|APG12L|FBR93|HAPG12 HGNC:588|MIM:609608|Ensembl:ENSG00000145782|HPRD:08496|Vega:OTTHUMG00000128889 5 5q21-q22 autophagy related 12 protein-coding autophagy related 12 We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 129 miR-181a hsa-miR-181a-5p,hsa-miR-181a-2-3p,hsa-miR-181a-3p MIMAT0000270,MIMAT0004558,MIMAT0000256 miRNA ATG16L1 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 55054 APG16L|ATG16A|ATG16L|IBD10|WDR30 HGNC:21498|MIM:610767|Ensembl:ENSG00000085978|HPRD:16498|Vega:OTTHUMG00000133619 2 2q37.1 autophagy related 16-like 1 (S. cerevisiae) protein-coding autophagy related 16-like 1 (S. cerevisiae) We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 130 miR-181a hsa-miR-181a-5p,hsa-miR-181a-2-3p,hsa-miR-181a-3p MIMAT0000270,MIMAT0004558,MIMAT0000256 miRNA ATG5 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 9474 APG5|APG5-LIKE|APG5L|ASP|hAPG5 HGNC:589|MIM:604261|Ensembl:ENSG00000057663|HPRD:16051|Vega:OTTHUMG00000016193 6 6q21 autophagy related 5 protein-coding autophagy related 5 We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 131 miR-181a hsa-miR-181a-5p,hsa-miR-181a-3p,hsa-miR-181a-2-3p MIMAT0000256,MIMAT0000270,MIMAT0004558 miRNA ATG5 autophagy down Homo sapiens 22902544 9606 9474 APG5|APG5-LIKE|APG5L|ASP|hAPG5 HGNC:589|MIM:604261|Ensembl:ENSG00000057663|HPRD:16051|Vega:OTTHUMG00000016193 6 6q21 autophagy related 5 protein-coding autophagy related 5 ATG5-ATG12 forms a large multimeric complex with ATG16, which functions as the E3 ligase for LC3. Several miRNA regulators of this step have been identified including miR-30a, miR-181a and miR-374a (ATG5), miR-630 (ATG12), miR-376b (ATG4), miR-204 (LC3), miR-375 (ATG7), miR-519a (ATG10 and ATG16), miR-885-3p (ATG16) and miR-101 (ATG4 and RAB5A). 132 miR-181a hsa-miR-181a-5p,hsa-miR-181a-2-3p,hsa-miR-181a-3p MIMAT0000270,MIMAT0004558,MIMAT0000256 miRNA ATG5 autophagy down Homo sapiens MCF-7/Huh-7/K562 cell 23322078 9606 9474 APG5|APG5-LIKE|APG5L|ASP|hAPG5 HGNC:589|MIM:604261|Ensembl:ENSG00000057663|HPRD:16051|Vega:OTTHUMG00000016193 6 6q21 autophagy related 5 protein-coding autophagy related 5 We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 133 miR-181a hsa-miR-181a-5p,hsa-miR-181a-3p,hsa-miR-181a-2-3p MIMAT0000256,MIMAT0000270,MIMAT0004558 miRNA BECN1 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 134 miR-181a hsa-miR-181a-5p,hsa-miR-181a-3p,hsa-miR-181a-2-3p MIMAT0000256,MIMAT0000270,MIMAT0004558 miRNA TP63 autophagy down Homo sapiens squamous cell carcinoma cell 22356768 9606 8626 AIS|B(p51A)|B(p51B)|EEC3|KET|LMS|NBP|OFC8|RHS|SHFM4|TP53CP|TP53L|TP73L|p40|p51|p53CP|p63|p73H|p73L HGNC:15979|MIM:603273|Ensembl:ENSG00000073282|HPRD:04469|Vega:OTTHUMG00000156313 3 3q28 tumor protein p63 protein-coding tumor protein p63 We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 135 miR-181a hsa-miR-181a-5p,hsa-miR-181a-3p,hsa-miR-181a-2-3p MIMAT0000256,MIMAT0000270,MIMAT0004558 miRNA UVRAG autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 7405 DHTX|VPS38|p63 HGNC:12640|MIM:602493|HPRD:03929 11 11q13.5 UV radiation resistance associated protein-coding UV radiation resistance associated We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 136 miR-182 hsa-miR-182-5p,hsa-miR-182-3p MIMAT0000259,MIMAT0000260 miRNA BCL2 autophagy down Homo sapiens prostate cancer cell 23936432 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 miR-182 expression in PC3 cells was also increased in response to stress induced by serum withdrawal, suggesting that miR-182 upregulation can occur due to nutritional stress. Bcl2 and p21 were identified to be potential target genes of miR-182 in PC3 cells. 137 miR-182 hsa-miR-182-5p,hsa-miR-182-3p MIMAT0000259,MIMAT0000260 miRNA CDKN1A autophagy down Homo sapiens PC3 23936432 9606 1026 CAP20|CDKN1|CIP1|MDA-6|P21|SDI1|WAF1|p21CIP1 HGNC:1784|MIM:116899|Ensembl:ENSG00000124762|HPRD:00298|Vega:OTTHUMG00000014603 6 6p21.2 cyclin-dependent kinase inhibitor 1A (p21, Cip1) protein-coding cyclin-dependent kinase inhibitor 1A (p21, Cip1) miR-182 expression in PC3 cells was also increased in response to stress induced by serum withdrawal, suggesting that miR-182 upregulation can occur due to nutritional stress. Bcl2 and p21 were identified to be potential target genes of miR-182 in PC3 cells. 138 miR-183 hsa-miR-183-5p,hsa-miR-183-3p MIMAT0000261,MIMAT0004560 miRNA autophagy Homo sapiens 22342941 9606 In this review, we focus on highlighting the dual functions of miRNAs as either oncogenes (e.g., miRNA-183, miRNA-376b, miRNA-106a, miRNA-221/222, miRNA-31 and miRNA-34c) or tumor suppressors (e.g., miRNA-30a, miRNA-101 and miRNA-9*) via mediating several autophagic signaling pathways in cancer pathogenesis. Taken together, these findings may uncover the regulatory mechanisms of oncogenic and tumor suppressive miRNAs in autophagy, which would provide a better understanding of miRNA-modulated autophagic signaling networks for future cancer therapeutics. 139 miR-18a hsa-miR-18a-5p,hsa-miR-18a-3p MIMAT0000072,MIMAT0002891 miRNA ATM autophagy up Homo sapiens colon cancer cells 23229340 9606 472 AT1|ATA|ATC|ATD|ATDC|ATE|TEL1|TELO1 HGNC:795|MIM:607585|Ensembl:ENSG00000149311|HPRD:06347|Vega:OTTHUMG00000166480 11 11q22-q23 ATM serine/threonine kinase protein-coding ATM serine/threonine kinase MicroRNA-18a upregulates autophagy and ataxia telangiectasia mutated gene expression in HCT116 colon cancer cells.Results of the present study pertaining to the role of miR-18a in regulating autophagy and ATM gene expression in colon cancer cells revealed a novel function for miR-18a in a critical cellular event and on a crucial gene with significant impacts in cancer development, progression, treatment and in other diseases. 140 miR-191 hsa-miR-191-5p,hsa-miR-191-3p MIMAT0000440,MIMAT0001618 miRNA BECN1 autophagy up Homo sapiens lung cancer cell 25685068 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related Increased Beclin-1, LC3-II and decreased p62 have been observed in radiation-resistant cells indicating elevated autophagy level. Decreased miR-191 in radiation-resistant cells performed by Taqman qRT-PCR also has been seen. Two binding sites between Beclin-1 and miR-191 suggest potential association between. 141 miR-195 hsa-miR-195-5p,hsa-miR-195-3p MIMAT0000461,MIMAT0004615 miRNA ATG14 autophagy Homo sapiens peripheral nerve cell 23361941 9606 22863 ATG14L|BARKOR|KIAA0831 HGNC:19962|MIM:613515|Ensembl:ENSG00000126775|HPRD:13820|Vega:OTTHUMG00000172129 14 14q22.3 autophagy related 14 protein-coding autophagy related 14 We further demonstrated that PNI significantly inhibited microglial autophagy activation, whereas miR-195 inhibitor treatment increased autophagy activation and suppressed neuroinflammation in vivo and in vitro. More important, autophagy inhibition impaired miR-195 inhibitor-induced downregulation of neuroinflammation and neuropathic pain. Additionally, ATG14 was identified as the functional target of miR-195. 142 miR-199a-5p hsa-miR-199a-5p MIMAT0000231 miRNA ATG7 autophagy Homo sapiens hepatocellular carcinoma cell 22713463 9606 10533 APG7-LIKE|APG7L|GSA7 HGNC:16935|MIM:608760|Ensembl:ENSG00000197548|HPRD:12293|Vega:OTTHUMG00000129740 3 3p25.3 autophagy related 7 protein-coding autophagy related 7 We further demonstrated that downregulated miR-199a-5p enhanced autophagy activation by targeting autophagy-associated gene 7 (ATG7). More important, autophagy inhibition abrogated miR-199a-5p downregulation-induced cell proliferation. 143 miR-199a-5p hsa-miR-199a-5p MIMAT0000231 miRNA BECN1 autophagy down Homo sapiens breast cancer cell. 23337876 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related Overexpression of miR-199a-5p inhibits DRAM1 and Beclin1 expression in MCF7 cells, while it enhances expression of these genes in MDA-MB-231 cells. 144 miR-199a-5p hsa-miR-199a-5p MIMAT0000231 miRNA DRAM1 autophagy down Homo sapiens breast cancer cell. 23337876 9606 55332 DRAM HGNC:25645|MIM:610776|Ensembl:ENSG00000136048|HPRD:07743|Vega:OTTHUMG00000170447 12 12q23.2 DNA-damage regulated autophagy modulator 1 protein-coding DNA-damage regulated autophagy modulator 1 Overexpression of miR-199a-5p inhibits DRAM1 and Beclin1 expression in MCF7 cells, while it enhances expression of these genes in MDA-MB-231 cells. 145 miR-19b hsa-miR-19b-3p MIMAT0000074 miRNA ATG7 autophagy down Homo sapiens hepatocellular carcinoma 25617127 9606 10533 APG7-LIKE|APG7L|GSA7 HGNC:16935|MIM:608760|Ensembl:ENSG00000197548|HPRD:12293|Vega:OTTHUMG00000129740 3 3p25.3 autophagy related 7 protein-coding autophagy related 7 The overexpressed PTENP1 decoyed oncomirs miR-17, miR-19b and miR-20a, which would otherwise target PTEN, PHLPP (a negative AKT regulator) and such autophagy genes as ULK1, ATG7 and p62, indicating that PTENP1 modulated the HCC cell behavior and gene networks by miRNA regulation. 146 miR-19b hsa-miR-19b-3p MIMAT0000074 miRNA SQSTM1 autophagy down Homo sapiens hepatocellular carcinoma 25617127 9606 8878 A170|OSIL|PDB3|ZIP3|p60|p62|p62B HGNC:11280|MIM:601530|Ensembl:ENSG00000161011|HPRD:03319|Vega:OTTHUMG00000150643 5 5q35 sequestosome 1 protein-coding sequestosome 1 The overexpressed PTENP1 decoyed oncomirs miR-17, miR-19b and miR-20a, which would otherwise target PTEN, PHLPP (a negative AKT regulator) and such autophagy genes as ULK1, ATG7 and p62, indicating that PTENP1 modulated the HCC cell behavior and gene networks by miRNA regulation. 147 miR-19b hsa-miR-19b-3p MIMAT0000074 miRNA ULK1 autophagy down Homo sapiens hepatocellular carcinoma 25617127 9606 8408 ATG1|ATG1A|UNC51|Unc51.1|hATG1 HGNC:12558|MIM:603168|Ensembl:ENSG00000177169|HPRD:11933|Vega:OTTHUMG00000168052 12 12q24.3 unc-51 like autophagy activating kinase 1 protein-coding unc-51 like autophagy activating kinase 1 The overexpressed PTENP1 decoyed oncomirs miR-17, miR-19b and miR-20a, which would otherwise target PTEN, PHLPP (a negative AKT regulator) and such autophagy genes as ULK1, ATG7 and p62, indicating that PTENP1 modulated the HCC cell behavior and gene networks by miRNA regulation. 148 miR-20 hsa-miR-20a-3p,hsa-miR-20b-3p MIMAT0004493,MIMAT0004752 miRNA SQSTM1 autophagy up Homo sapiens myeloid 32D cells 22441107 9606 8878 A170|OSIL|PDB3|ZIP3|p60|p62|p62B HGNC:11280|MIM:601530|Ensembl:ENSG00000161011|HPRD:03319|Vega:OTTHUMG00000150643 5 5q35 sequestosome 1 protein-coding sequestosome 1 SQSTM1 (sequestosome 1/p62), a multiple domain protein that acts as a signaling hub, was identified as a key target for these miRNAs. SQSTM1 can interfere with autophagy via binding to the autophagic regulator Atg8/LC3. 149 miR-200c hsa-miR-200c-3p,hsa-miR-200c-5p MIMAT0000617,MIMAT0004657 miRNA UBQLN1 autophagy down Homo sapiens breast cancer cell 25044403 9606 29979 DA41|DSK2|PLIC-1|UBQN|XDRP1 HGNC:12508|MIM:605046|Ensembl:ENSG00000135018|HPRD:05440|Vega:OTTHUMG00000020104 9 9q22|9q21.2-q21.3 ubiquilin 1 protein-coding ubiquilin 1 MiR-200c inhibits autophagy and enhances radiosensitivity in breast cancer cells by targeting UBQLN1. 150 miR-204 hsa-miR-204-5p,hsa-miR-204-3p MIMAT0000265,MIMAT0022693 miRNA CAV1 autophagy up Homo sapiens renal cell carcinoma 25517751 9606 857 BSCL3|CGL3|LCCNS|MSTP085|PPH3|VIP21 HGNC:1527|MIM:601047|Ensembl:ENSG00000105974|HPRD:03028|Vega:OTTHUMG00000023413 7 7q31.1 caveolin 1, caveolae protein, 22kDa protein-coding caveolin 1, caveolae protein, 22kDa The von Hippel-Lindau tumor suppressor (VHL) represses TRPM3 directly through miR-204 and indirectly through another miR-204 target, Caveolin 1 (CAV1). 151 miR-204 hsa-miR-204-5p,hsa-miR-204-3p MIMAT0000265,MIMAT0022693 miRNA MAP1LC3B autophagy down Homo sapiens cardiomyocyte 21631941 9606 81631 ATG8F|LC3B|MAP1A/1BLC3|MAP1LC3B-a HGNC:13352|MIM:609604|Ensembl:ENSG00000140941|HPRD:14358|Vega:OTTHUMG00000137654 16 16q24.2 microtubule-associated protein 1 light chain 3 beta protein-coding microtubule-associated protein 1 light chain 3 beta We found that IR induced cardiomyocytes autophagy, together with down-regulation of miR-204 and up-regulation of LC3-II protein. And, we have found that LC3-II protein was regulated by miR-204, using the method of transferring miR-204 mimic or AMO-204 into the cardiomyocytes, before. 152 miR-204 hsa-miR-204-5p,hsa-miR-204-3p MIMAT0000265,MIMAT0022693 miRNA TRPM3 autophagy down Homo sapiens renal cell carcinoma 25517751 9606 80036 GON-2|LTRPC3|MLSN2 HGNC:17992|MIM:608961|Ensembl:ENSG00000083067|HPRD:10605|Vega:OTTHUMG00000019997 9 9q21.12 transient receptor potential cation channel, subfamily M, member 3 protein-coding transient receptor potential cation channel, subfamily M, member 3 The von Hippel-Lindau tumor suppressor (VHL) represses TRPM3 directly through miR-204 and indirectly through another miR-204 target, Caveolin 1 (CAV1). 153 miR-204 hsa-miR-204-5p,hsa-miR-204-3p MIMAT0000265,MIMAT0022693 miRNA VHL autophagy down Homo sapiens renal cell carcinoma 25517751 9606 7428 HRCA1|RCA1|VHL1|pVHL HGNC:12687|MIM:608537|HPRD:01905 3 3p25.3 von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase protein-coding von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase The von Hippel-Lindau tumor suppressor (VHL) represses TRPM3 directly through miR-204 and indirectly through another miR-204 target, Caveolin 1 (CAV1). 154 miR-204 hsa-miR-204-5p,hsa-miR-204-3p MIMAT0000265,MIMAT0022693 miRNA autophagy Homo sapiens 21293178 9606 MicroRNA enrichment analysis revealed miR-130, 98, 124, 204 and 142 as the putative post-transcriptional regulators of the autophagy-lysosomal pathway genes. 155 miR-204 hsa-miR-204-5p,hsa-miR-204-3p MIMAT0000265,MIMAT0022693 miRNA autophagy Homo sapiens renal clear cell 23141280 9606 VHL-Regulated miR-204 suppresses tumor growth through inhibition of LC3B-mediated autophagy in renal clear cell carcinoma. 156 miR-204-5p hsa-miR-204-5p MIMAT0000265 miRNA MAP1LC3B autophagy down Homo sapiens colorectal cancer cell 25209181 9606 81631 ATG8F|LC3B|MAP1A/1BLC3|MAP1LC3B-a HGNC:13352|MIM:609604|Ensembl:ENSG00000140941|HPRD:14358|Vega:OTTHUMG00000137654 16 16q24.2 microtubule-associated protein 1 light chain 3 beta protein-coding microtubule-associated protein 1 light chain 3 beta This may be explained by the fact that miR-204-5p increases in colorectal cancer cases in order to inhibit increased activity of LC3B-II in autophagy and Bcl2 against apoptosis posttranscriptionally and to take role as tumor suppressor. 157 miR-205 hsa-miR-205-5p,hsa-miR-205-3p MIMAT0000266,MIMAT0009197 miRNA LAMP3 autophagy down Homo sapiens prostate cancer cell 24370341 9606 27074 CD208|DC LAMP|DC-LAMP|DCLAMP|LAMP|LAMP-3|TSC403 HGNC:14582|MIM:605883|Ensembl:ENSG00000078081|HPRD:12062|Vega:OTTHUMG00000158387 3 3q26.3-q27 lysosomal-associated membrane protein 3 protein-coding lysosomal-associated membrane protein 3 Specifically, the constraints on the autophagic flux were associated to the miRNA-dependent down-regulation of the lysosome-associated proteins RAB27A and LAMP3. These findings suggest that miR-205-mediated impairment of the autophagic pathway may interfere with the detoxifying capabilities of prostate cancer cells in their attempt to cope with cisplatin-induced detrimental effects. 158 miR-205 hsa-miR-205-5p,hsa-miR-205-3p MIMAT0000266,MIMAT0009197 miRNA RAB27A autophagy down Homo sapiens prostate cancer cell 24370341 9606 5873 GS2|HsT18676|RAB27|RAM HGNC:9766|MIM:603868|Ensembl:ENSG00000069974|HPRD:04845|Vega:OTTHUMG00000131959 15 15q15-q21.1 RAB27A, member RAS oncogene family protein-coding RAB27A, member RAS oncogene family Specifically, the constraints on the autophagic flux were associated to the miRNA-dependent down-regulation of the lysosome-associated proteins RAB27A and LAMP3. These findings suggest that miR-205-mediated impairment of the autophagic pathway may interfere with the detoxifying capabilities of prostate cancer cells in their attempt to cope with cisplatin-induced detrimental effects. 159 miR-20a hsa-miR-20a-5p,hsa-miR-20a-3p MIMAT0000075,MIMAT0004493 miRNA ATG7 autophagy down Homo sapiens hepatocellular carcinoma 25617127 9606 10533 APG7-LIKE|APG7L|GSA7 HGNC:16935|MIM:608760|Ensembl:ENSG00000197548|HPRD:12293|Vega:OTTHUMG00000129740 3 3p25.3 autophagy related 7 protein-coding autophagy related 7 The overexpressed PTENP1 decoyed oncomirs miR-17, miR-19b and miR-20a, which would otherwise target PTEN, PHLPP (a negative AKT regulator) and such autophagy genes as ULK1, ATG7 and p62, indicating that PTENP1 modulated the HCC cell behavior and gene networks by miRNA regulation. 160 miR-20a hsa-miR-20a-5p,hsa-miR-20a-3p MIMAT0000075,MIMAT0004493 miRNA SQSTM1 autophagy down Homo sapiens hepatocellular carcinoma 25617127 9606 8878 A170|OSIL|PDB3|ZIP3|p60|p62|p62B HGNC:11280|MIM:601530|Ensembl:ENSG00000161011|HPRD:03319|Vega:OTTHUMG00000150643 5 5q35 sequestosome 1 protein-coding sequestosome 1 The overexpressed PTENP1 decoyed oncomirs miR-17, miR-19b and miR-20a, which would otherwise target PTEN, PHLPP (a negative AKT regulator) and such autophagy genes as ULK1, ATG7 and p62, indicating that PTENP1 modulated the HCC cell behavior and gene networks by miRNA regulation. 161 miR-20a hsa-miR-20a-5p,hsa-miR-20a-3p MIMAT0000075,MIMAT0004493 miRNA ULK1 autophagy down Homo sapiens myoblast cell line cells 22781751 9606 8408 ATG1|ATG1A|UNC51|Unc51.1|hATG1 HGNC:12558|MIM:603168|Ensembl:ENSG00000177169|HPRD:11933|Vega:OTTHUMG00000168052 12 12q24.3 unc-51 like autophagy activating kinase 1 protein-coding unc-51 like autophagy activating kinase 1 MiR-20a and miR-106b negatively regulate autophagy induced by leucine deprivation via suppression of ULK1 expression in C2C12 myoblasts. 162 miR-20a hsa-miR-20a-5p,hsa-miR-20a-3p MIMAT0000075,MIMAT0004493 miRNA ULK1 autophagy down Homo sapiens hepatocellular carcinoma 25617127 9606 8408 ATG1|ATG1A|UNC51|Unc51.1|hATG1 HGNC:12558|MIM:603168|Ensembl:ENSG00000177169|HPRD:11933|Vega:OTTHUMG00000168052 12 12q24.3 unc-51 like autophagy activating kinase 1 protein-coding unc-51 like autophagy activating kinase 1 The overexpressed PTENP1 decoyed oncomirs miR-17, miR-19b and miR-20a, which would otherwise target PTEN, PHLPP (a negative AKT regulator) and such autophagy genes as ULK1, ATG7 and p62, indicating that PTENP1 modulated the HCC cell behavior and gene networks by miRNA regulation. 163 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA AKT1 autophagy down Homo sapiens malignant glioma cell line cells 23077620 9606 207 AKT|CWS6|PKB|PKB-ALPHA|PRKBA|RAC|RAC-ALPHA HGNC:391|MIM:164730|Ensembl:ENSG00000142208|HPRD:01261|Vega:OTTHUMG00000170795 14 14q32.32 v-akt murine thymoma viral oncogene homolog 1 protein-coding v-akt murine thymoma viral oncogene homolog 1 Silencing of microRNA-21 confers radio-sensitivity through inhibition of the PI3K/AKT pathway and enhancing autophagy in malignant glioma cell lines. 164 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA BCL2 autophagy down Homo sapiens colon cancer 25385144 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 The inhibition of HIF-1¦Á decreased miR-210 expression and autophagy. Silencing of miR-210 upregulated Bcl-2 expression and reduced the survival fraction of colon cancer cells after radiation treatment. Under hypoxia, HIF-1¦Á induces miRNA-210 which in turn enhances autophagy and reduces radiosensitivity by downregulating Bcl-2 expression in colon cancer cells. 165 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA HIF1A autophagy up Homo sapiens colon cancer 25385144 9606 3091 HIF-1A|HIF-1alpha|HIF1|HIF1-ALPHA|MOP1|PASD8|bHLHe78 HGNC:4910|MIM:603348|Ensembl:ENSG00000100644|HPRD:04517|Vega:OTTHUMG00000140344 14 14q23.2 hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) protein-coding hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) The inhibition of HIF-1¦Á decreased miR-210 expression and autophagy. Silencing of miR-210 upregulated Bcl-2 expression and reduced the survival fraction of colon cancer cells after radiation treatment. Under hypoxia, HIF-1¦Á induces miRNA-210 which in turn enhances autophagy and reduces radiosensitivity by downregulating Bcl-2 expression in colon cancer cells. 166 miR-214 hsa-miR-204-5p,hsa-miR-204-3p MIMAT0000265,MIMAT0022693 miRNA MAP1LC3A autophagy down Homo sapiens renal cell carcinoma 25517751 9606 84557 ATG8E|LC3|LC3A|MAP1ALC3|MAP1BLC3 HGNC:6838|MIM:601242|Ensembl:ENSG00000101460|HPRD:03144|Vega:OTTHUMG00000032306 20 20q11.22 microtubule-associated protein 1 light chain 3 alpha protein-coding microtubule-associated protein 1 light chain 3 alpha Increased expression of TRPM3 in RCC leads to Ca(2+) influx, activation of CAMKK2, AMPK, and ULK1, and phagophore formation. In addition, TRPM3 Ca(2+) and Zn(2+) fluxes inhibit miR-214, which directly targets LC3A and LC3B. 167 miR-214 hsa-miR-204-5p,hsa-miR-204-3p MIMAT0000265,MIMAT0022693 miRNA MAP1LC3B autophagy down Homo sapiens renal cell carcinoma 25517751 9606 81631 ATG8F|LC3B|MAP1A/1BLC3|MAP1LC3B-a HGNC:13352|MIM:609604|Ensembl:ENSG00000140941|HPRD:14358|Vega:OTTHUMG00000137654 16 16q24.2 microtubule-associated protein 1 light chain 3 beta protein-coding microtubule-associated protein 1 light chain 3 beta Increased expression of TRPM3 in RCC leads to Ca(2+) influx, activation of CAMKK2, AMPK, and ULK1, and phagophore formation. In addition, TRPM3 Ca(2+) and Zn(2+) fluxes inhibit miR-214, which directly targets LC3A and LC3B. 168 miR-214 hsa-miR-204-5p,hsa-miR-204-3p MIMAT0000265,MIMAT0022693 miRNA TRPM3 autophagy down Homo sapiens renal cell carcinoma 25517751 9606 80036 GON-2|LTRPC3|MLSN2 HGNC:17992|MIM:608961|Ensembl:ENSG00000083067|HPRD:10605|Vega:OTTHUMG00000019997 9 9q21.12 transient receptor potential cation channel, subfamily M, member 3 protein-coding transient receptor potential cation channel, subfamily M, member 3 Increased expression of TRPM3 in RCC leads to Ca(2+) influx, activation of CAMKK2, AMPK, and ULK1, and phagophore formation. In addition, TRPM3 Ca(2+) and Zn(2+) fluxes inhibit miR-214, which directly targets LC3A and LC3B. 169 miR-216a hsa-miR-216a-5p,hsa-miR-216a-3p MIMAT0000273,MIMAT0022844 miRNA ATG5 autophagy down Homo sapiens umbilical vein endothelial cell 24481443 9606 9474 APG5|APG5-LIKE|APG5L|ASP|hAPG5 HGNC:589|MIM:604261|Ensembl:ENSG00000057663|HPRD:16051|Vega:OTTHUMG00000016193 6 6q21 autophagy related 5 protein-coding autophagy related 5 We found that in young HUVECs, miR-216a overexpression repressed BECN1 and ATG5 expression and the ox-LDL induced autophagy, as evaluated by microtubule-associated protein 1 light chain 3 (LC3B) analysis and cytofluorimetric assay. 170 miR-216a hsa-miR-216a-5p,hsa-miR-216a-3p MIMAT0000273,MIMAT0022844 miRNA BECN1 autophagy down Homo sapiens umbilical vein endothelial cell 24481443 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related We found that in young HUVECs, miR-216a overexpression repressed BECN1 and ATG5 expression and the ox-LDL induced autophagy, as evaluated by microtubule-associated protein 1 light chain 3 (LC3B) analysis and cytofluorimetric assay. 171 miR-216a hsa-miR-216a-5p,hsa-miR-216a-3p MIMAT0000273,MIMAT0022844 miRNA LDLR autophagy down Homo sapiens umbilical vein endothelial cell 24481443 9606 3949 FH|FHC|LDLCQ2 HGNC:6547|MIM:606945|Ensembl:ENSG00000130164|HPRD:06091|Vega:OTTHUMG00000171935 19 19p13.2 low density lipoprotein receptor protein-coding low density lipoprotein receptor We found that in young HUVECs, miR-216a overexpression repressed BECN1 and ATG5 expression and the ox-LDL induced autophagy, as evaluated by microtubule-associated protein 1 light chain 3 (LC3B) analysis and cytofluorimetric assay. 172 miR-216b hsa-miR-216b-5p,hsa-miR-216b-5p MIMAT0004959,MIMAT0026721 miRNA BECN1 autophagy down Homo sapiens Tenon's fibroblasts 24681041 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related Further, we showed that miR-216b could directly target a specific fragment in the 3' untranslated region of Beclin 1 as demonstrated by luciferase assay, and consequently decreased the expression of Beclin 1. Consistently, knocking down Beclin 1 significantly decreased HCPT-triggered autophagy and apoptosis, and increased the viability of HTFs treated with HCPT, 173 miR-22 hsa-miR-22-5p,hsa-miR-22-3p MIMAT0004495,MIMAT0000077 miRNA HMGB1 autophagy down Homo sapiens osteosarcoma cells 24609901 9606 3146 HMG1|HMG3|SBP-1 HGNC:4983|MIM:163905|Ensembl:ENSG00000189403|HPRD:01228|Vega:OTTHUMG00000016670 13 13q12 high mobility group box 1 protein-coding high mobility group box 1 However, possibly as a compensatory effect, miR-22 was also upregulatedduring the chemotherapy, and the overexpressed miR-22 targeted the 3' UTR of HMGB1 and inhibits the HMGB1-promoted autophagy. 174 miR-22 hsa-miR-22-5p,hsa-miR-22-3p MIMAT0004495,MIMAT0000077 miRNA HMGB1 autophagy down Homo sapiens osteosarcoma cells 24752578 9606 3146 HMG1|HMG3|SBP-1 HGNC:4983|MIM:163905|Ensembl:ENSG00000189403|HPRD:01228|Vega:OTTHUMG00000016670 13 13q12 high mobility group box 1 protein-coding high mobility group box 1 Results demonstrated that miR-22 well paired with the 3'-UTR of HMGB1 downregulated the HMGB1 expression and blocked the HMGB1-mediated autophagy during chemotherapy in osteosarcoma cells in vitro. 175 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA CDK2 autophagy down Homo sapiens cardiomyocytes 25394488 9606 1017 CDKN2|p33(CDK2) HGNC:1771|MIM:116953|Ensembl:ENSG00000123374|HPRD:00310|Vega:OTTHUMG00000170575 12 12q13 cyclin-dependent kinase 2 protein-coding cyclin-dependent kinase 2 MicroRNA-221 inhibits autophagy and promotes heart failure by modulating the p27/CDK2/mTOR axis. 176 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA CDKN1B autophagy down Homo sapiens cardiomyocytes 25394488 9606 1027 CDKN4|KIP1|MEN1B|MEN4|P27KIP1 HGNC:1785|MIM:600778|Ensembl:ENSG00000111276|HPRD:02867|Vega:OTTHUMG00000149914 12 12p13.1-p12 cyclin-dependent kinase inhibitor 1B (p27, Kip1) protein-coding cyclin-dependent kinase inhibitor 1B (p27, Kip1) MicroRNA-221 inhibits autophagy and promotes heart failure by modulating the p27/CDK2/mTOR axis. 177 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA MTOR autophagy up Homo sapiens cardiomyocytes 25394488 9606 2475 FRAP|FRAP1|FRAP2|RAFT1|RAPT1 HGNC:3942|MIM:601231|Ensembl:ENSG00000198793|HPRD:03134|Vega:OTTHUMG00000002001 1 1p36.2 mechanistic target of rapamycin (serine/threonine kinase) protein-coding mechanistic target of rapamycin (serine/threonine kinase) MicroRNA-221 inhibits autophagy and promotes heart failure by modulating the p27/CDK2/mTOR axis. 178 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA autophagy Homo sapiens 22342941 9606 In this review, we focus on highlighting the dual functions of miRNAs as either oncogenes (e.g., miRNA-183, miRNA-376b, miRNA-106a, miRNA-221/222, miRNA-31 and miRNA-34c) or tumor suppressors (e.g., miRNA-30a, miRNA-101 and miRNA-9*) via mediating several autophagic signaling pathways in cancer pathogenesis. Taken together, these findings may uncover the regulatory mechanisms of oncogenic and tumor suppressive miRNAs in autophagy, which would provide a better understanding of miRNA-modulated autophagic signaling networks for future cancer therapeutics. 179 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA autophagy Homo sapiens breast cancer cell 23529451 9606 Here, we review the role of miR-221/222 in breast cancer (BCa) development and progression: regulating proliferative signaling pathways, altering telomere and telomerase activity, avoiding cell death from tumor suppressors, autophagy and apoptosis, monitoring angiogenesis, supporting epithelial-mesenchymal transition, and even controlling cell-specific function within microenvironment. 180 miR-222 hsa-miR-222-3p,hsa-miR-222-5p MIMAT0000279,MIMAT0004569 miRNA autophagy Homo sapiens 22342941 9606 In this review, we focus on highlighting the dual functions of miRNAs as either oncogenes (e.g., miRNA-183, miRNA-376b, miRNA-106a, miRNA-221/222, miRNA-31 and miRNA-34c) or tumor suppressors (e.g., miRNA-30a, miRNA-101 and miRNA-9*) via mediating several autophagic signaling pathways in cancer pathogenesis. Taken together, these findings may uncover the regulatory mechanisms of oncogenic and tumor suppressive miRNAs in autophagy, which would provide a better understanding of miRNA-modulated autophagic signaling networks for future cancer therapeutics. 181 miR-222 hsa-miR-222-3p,hsa-miR-222-5p MIMAT0000279,MIMAT0004569 miRNA autophagy Homo sapiens breast cancer cell 23529451 9606 Here, we review the role of miR-221/222 in breast cancer (BCa) development and progression: regulating proliferative signaling pathways, altering telomere and telomerase activity, avoiding cell death from tumor suppressors, autophagy and apoptosis, monitoring angiogenesis, supporting epithelial-mesenchymal transition, and even controlling cell-specific function within microenvironment. 182 miR-224 hsa-miR-224-5p,hsa-miR-224-3p MIMAT0009198,MIMAT0000281 miRNA SMAD4 autophagy down Homo sapiens hepatoma cell 23913306 9606 4089 DPC4|JIP|MADH4|MYHRS HGNC:6770|MIM:600993|Ensembl:ENSG00000141646|HPRD:02995|Vega:OTTHUMG00000132696 18 18q21.1 SMAD family member 4 protein-coding SMAD family member 4 our in vitro study demonstrated that miR-224 played an oncogenic role in hepatoma cell migration and tumor formation through silencing its target gene Smad4. 183 miR-224 hsa-miR-224-5p,hsa-miR-224-3p MIMAT0000281,MIMAT0009198 miRNA SMAD4 autophagy down Homo sapiens hepatocellular carcinoma cell 25068270 9606 4089 DPC4|JIP|MADH4|MYHRS HGNC:6770|MIM:600993|Ensembl:ENSG00000141646|HPRD:02995|Vega:OTTHUMG00000132696 18 18q21.1 SMAD family member 4 protein-coding SMAD family member 4 Based on this finding, we further demonstrated that in hepatitis B virus (HBV)-related HCC, aberrant autophagy (low autophagic activity) results in accumulation of MIR224 and decreased expression of the target gene Smad4, which leads to increased cell migration and tumor formation. 184 miR-23b hsa-miR-23b-3p,hsa-miR-23b-5p MIMAT0000418,MIMAT0004587 miRNA ATG12 autophagy down Homo sapiens pancreatic 23916944 9606 9140 APG12|APG12L|FBR93|HAPG12 HGNC:588|MIM:609608|Ensembl:ENSG00000145782|HPRD:08496|Vega:OTTHUMG00000128889 5 5q21-q22 autophagy related 12 protein-coding autophagy related 12 In pancreatic cancer cells, reduced levels of the miRNA miR-23b increase levels of ATG12 and autophagy to promote radioresistance. 185 miR-23b hsa-miR-23b-3p,hsa-miR-23b-5p MIMAT0000418,MIMAT0004587 miRNA ATG12 autophagy down Homo sapiens pancreatic cancer cell 24145177 9606 9140 APG12|APG12L|FBR93|HAPG12 HGNC:588|MIM:609608|Ensembl:ENSG00000145782|HPRD:08496|Vega:OTTHUMG00000128889 5 5q21-q22 autophagy related 12 protein-coding autophagy related 12 Here we demonstrated that MIR23B is a potent inhibitor of autophagy. MIR23B targets the 3-UTR of the autophagy-related gene ATG12, thereby decreasing autophagic activity and ultimately promoting radiation-induced pancreatic cancer cell death. 186 miR-24 hsa-miR-24-1-5p,hsa-miR-24-3p,hsa-miR-24-2-5p MIMAT0000079,MIMAT0000080,MIMAT0004497 miRNA autophagy Homo sapiens muscle cells 24063572 9606 In vitro, synthetic miR-24 overexpression had detrimental effects on SMC functional capacity inducing apoptosis, migration defects, enhanced autophagy, and loss of contractile marker genes. 187 miR-24-3p hsa-miR-24-3p MIMAT0000080 miRNA ATG4A autophagy down Homo sapiens SCLC cells 25426560 9606 115201 APG4A|AUTL2 HGNC:16489|MIM:300663|Ensembl:ENSG00000101844|HPRD:06455|Vega:OTTHUMG00000022176 X Xq22.1-q22.3 autophagy related 4A, cysteine peptidase protein-coding autophagy related 4A, cysteine peptidase We further found thatdownregulated miR-24-3p enhanced autophagy activation as it directly targets and inhibits autophagy-associated gene 4A (ATG4A). 188 miR-27 hsa-miR-27a-3p,hsa-miR-27a-5p,hsa-miR-27b-5p,hsa-miR-27b-3p MIMAT0000084,MIMAT0004501,MIMAT0004588,MIMAT0000419 miRNA autophagy Homo sapiens colon cancer 25526515 9606 We identified and selected four downregulated miRNAs including hsa-miR-302a-3p and 27 upregulated miRNAs under these two conditions as having the potential to target genes involved in the regulation of autophagy in human colon cancer cells. 189 miR-30 hsa-miR-30a-5p,hsa-miR-30a-3p,hsa-miR-30c-5p,hsa-miR-30d-5p,hsa-miR-30 MIMAT0000087,MIMAT0000088,MIMAT0000244,MIMAT000024 miRNA BECN1 autophagy down Homo sapiens cardiomyocyte cells 23326547 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related Angiotensin II induces down-regulation of miR-30 in cardiomyocytes, which in turn promotes myocardial hypertrophy through excessive autophagy. A dual luciferase reporter assay confirmed that beclin-1 was a target gene of miR-30a. 190 miR-302a-3p hsa-miR-302a-3p MIMAT0000684 miRNA autophagy Homo sapiens colon cancer 25526515 9606 We identified and selected four downregulated miRNAs including hsa-miR-302a-3p and 27 upregulated miRNAs under these two conditions as having the potential to target genes involved in the regulation of autophagy in human colon cancer cells. 191 miR-30a hsa-miR-30a-5p,hsa-miR-30a-3p MIMAT0000087,MIMAT0000088 miRNA ATG5 autophagy down Homo sapiens chronic myeloid leukemia cells 22395361 9606 9474 APG5|APG5-LIKE|APG5L|ASP|hAPG5 HGNC:589|MIM:604261|Ensembl:ENSG00000057663|HPRD:16051|Vega:OTTHUMG00000016193 6 6q21 autophagy related 5 protein-coding autophagy related 5 apoptosis specific protei miR-30a is a potent inhibitor of autophagy by downregulating Beclin 1 and ATG5 expression. 192 miR-30a hsa-miR-30a-5p,hsa-miR-30a-3p MIMAT0000087,MIMAT0000088 miRNA ATG5 autophagy down Homo sapiens chronic myelogenous leukemia cell 22617440 9606 9474 APG5|APG5-LIKE|APG5L|ASP|hAPG5 HGNC:589|MIM:604261|Ensembl:ENSG00000057663|HPRD:16051|Vega:OTTHUMG00000016193 6 6q21 autophagy related 5 protein-coding autophagy related 5 MIR30A, but not MIR101, is a potent inhibitor of autophagy by selectively downregulating BECN1 and ATG5 expression in CML cells. 193 miR-30a hsa-miR-30a-5p,hsa-miR-30a-3p MIMAT0000087,MIMAT0000088 miRNA ATG5 autophagy down Homo sapiens human chronic myeloid leukemia cells 22902544 9606 9474 APG5|APG5-LIKE|APG5L|ASP|hAPG5 HGNC:589|MIM:604261|Ensembl:ENSG00000057663|HPRD:16051|Vega:OTTHUMG00000016193 6 6q21 autophagy related 5 protein-coding autophagy related 5 ATG5-ATG12 forms a large multimeric complex with ATG16, which functions as the E3 ligase for LC3. Several miRNA regulators of this step have been identified including miR-30a, miR-181a and miR-374a (ATG5), miR-630 (ATG12), miR-376b (ATG4), miR-204 (LC3), miR-375 (ATG7), miR-519a (ATG10 and ATG16), miR-885-3p (ATG16) and miR-101 (ATG4 and RAB5A). 194 miR-30a hsa-miR-30a-5p,hsa-miR-30a-3p MIMAT0000087,MIMAT0000088 miRNA BECN1 autophagy down Homo sapiens breast cancer cells 19535919 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related ATG6 autophagy related 6 Beclin 1 is a potential target for miRNA miR-30a, and this miRNA could negatively regulate beclin 1 expression resulting in decreased autophagic activity. 195 miR-30a hsa-miR-30a-5p,hsa-miR-30a-3p MIMAT0000087,MIMAT0000088 miRNA BECN1 autophagy down Homo sapiens breast cancer cells 22157765 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related MicroRNA-30a sensitizes tumor cells to cis-platinum via suppressing beclin 1-mediated autophagy. 196 miR-30a hsa-miR-30a-5p,hsa-miR-30a-3p MIMAT0000087,MIMAT0000088 miRNA BECN1 autophagy down Homo sapiens chronic myelogenous leukemia cell 22617440 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related MIR30A, but not MIR101, is a potent inhibitor of autophagy by selectively downregulating BECN1 and ATG5 expression in CML cells. 197 miR-30a hsa-miR-30a-5p,hsa-miR-30a-3p MIMAT0000087,MIMAT0000088 miRNA BECN1 autophagy down Homo sapiens human chronic myeloid leukemia cells 22902544 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related ATG5-ATG12 forms a large multimeric complex with ATG16, which functions as the E3 ligase for LC3. Several miRNA regulators of this step have been identified including miR-30a, miR-181a and miR-374a (ATG5), miR-630 (ATG12), miR-376b (ATG4), miR-204 (LC3), miR-375 (ATG7), miR-519a (ATG10 and ATG16), miR-885-3p (ATG16) and miR-101 (ATG4 and RAB5A). 198 miR-30a hsa-miR-30a-5p,hsa-miR-30a-3p MIMAT0000087,MIMAT0000088 miRNA BECN1 autophagy down Homo sapiens H9c2 cell 23660952 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related Downregulated miR-30a activated autophagy by inhibiting beclin-1 expression in H9c2 cell. More important, autophagy inhibition suppressed miR-30a inhibitor-induced cardiomyocyte hypertrophy. 199 miR-30a hsa-miR-30a-5p,hsa-miR-30a-3p MIMAT0000087,MIMAT0000088 miRNA BECN1 autophagy Homo sapiens hepatic cell 25620738 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related To confirm these findings, HBx and miRNA-30a were coexpressed in HepG2 cells, and the results showed significant inhibition of autophagosome formation and beclin-1 and c-myc expression, 200 miR-30a hsa-miR-30a-5p,hsa-miR-30a-3p MIMAT0000087,MIMAT0000088 miRNA MYC autophagy down Homo sapiens hepatic cell 25620738 9606 4609 MRTL|MYCC|bHLHe39|c-Myc HGNC:7553|MIM:190080|Ensembl:ENSG00000136997|HPRD:01818|Vega:OTTHUMG00000128475 8 8q24.21 v-myc avian myelocytomatosis viral oncogene homolog protein-coding v-myc avian myelocytomatosis viral oncogene homolog To confirm these findings, HBx and miRNA-30a were coexpressed in HepG2 cells, and the results showed significant inhibition of autophagosome formation and beclin-1 and c-myc expression, 201 miR-30a hsa-miR-30a-5p,hsa-miR-30a-3p MIMAT0000087,MIMAT0000088 miRNA autophagy Homo sapiens 22342941 9606 In this review, we focus on highlighting the dual functions of miRNAs as either oncogenes (e.g., miRNA-183, miRNA-376b, miRNA-106a, miRNA-221/222, miRNA-31 and miRNA-34c) or tumor suppressors (e.g., miRNA-30a, miRNA-101 and miRNA-9*) via mediating several autophagic signaling pathways in cancer pathogenesis. Taken together, these findings may uncover the regulatory mechanisms of oncogenic and tumor suppressive miRNAs in autophagy, which would provide a better understanding of miRNA-modulated autophagic signaling networks for future cancer therapeutics. 202 miR-30b hsa-miR-30b-5p,hsa-miR-30b-3p MIMAT0000420,MIMAT0004589 miRNA ATG12 autophagy down Homo sapiens stomach 22647547 9606 9140 APG12|APG12L|FBR93|HAPG12 HGNC:588|MIM:609608|Ensembl:ENSG00000145782|HPRD:08496|Vega:OTTHUMG00000128889 5 5q21-q22 autophagy related 12 protein-coding autophagy related 12 As a potential mechanistic explanation for this observation, we demonstrate that MIR30B directly targets ATG12 and BECN1, which are important proteins involved in autophagy. 203 miR-30b hsa-miR-30b-5p,hsa-miR-30b-3p MIMAT0000420,MIMAT0004589 miRNA BECN1 autophagy down Homo sapiens stomach 22647547 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related As a potential mechanistic explanation for this observation, we demonstrate that MIR30B directly targets ATG12 and BECN2, which are important proteins involved in autophagy. 204 miR-30c hsa-miR-30c-5p,hsa-miR-30c-2-3p,hsa-miR-30c-1-3p MIMAT0000244,MIMAT0004550,MIMAT0004674 miRNA ATG16L1 autophagy down Homo sapiens ileal biopsy 24148619 9606 55054 APG16L|ATG16A|ATG16L|IBD10|WDR30 HGNC:21498|MIM:610767|Ensembl:ENSG00000085978|HPRD:16498|Vega:OTTHUMG00000133619 2 2q37.1 autophagy related 16-like 1 (S. cerevisiae) protein-coding autophagy related 16-like 1 (S. cerevisiae) In ileal biopsy samples of patients with CD, there was an inverse correlation between levels of MIR30C and MIR130A and those of ATG5 and ATG16L1, supporting in vitro findings. Inhibition of MIR30C and MIR130A in cultured intestinal epithelial cells and in mouse enterocytes blocked AIEC-induced inhibition of ATG5 and ATG16L1 expression and restored functional autophagy. 205 miR-30c hsa-miR-30c-5p,hsa-miR-30c-2-3p,hsa-miR-30c-1-3p MIMAT0000244,MIMAT0004550,MIMAT0004674 miRNA ATG5 autophagy down Homo sapiens ileal biopsy 24148619 9606 9474 APG5|APG5-LIKE|APG5L|ASP|hAPG5 HGNC:589|MIM:604261|Ensembl:ENSG00000057663|HPRD:16051|Vega:OTTHUMG00000016193 6 6q21 autophagy related 5 protein-coding autophagy related 5 In ileal biopsy samples of patients with CD, there was an inverse correlation between levels of MIR30C and MIR130A and those of ATG5 and ATG16L1, supporting in vitro findings. Inhibition of MIR30C and MIR130A in cultured intestinal epithelial cells and in mouse enterocytes blocked AIEC-induced inhibition of ATG5 and ATG16L1 expression and restored functional autophagy. 206 mir-30d hsa-miR-30d-5p,hsa-miR-30d-3p MIMAT0000245,MIMAT0004551 miRNA ATG12 autophagy down Homo sapiens epithelial 23274497 9606 9140 APG12|APG12L|FBR93|HAPG12 HGNC:588|MIM:609608|Ensembl:ENSG00000145782|HPRD:08496|Vega:OTTHUMG00000128889 5 5q21-q22 autophagy related 12 protein-coding autophagy related 12 Using a combined bioinformatics approach, gene set enrichment analysis, and miRNA target prediction, we found that mir-30d might regulate multiple genes in the autophagy pathway including BECN1, BNIP3L, ATG12, ATG5, and ATG2. 207 miR-30d hsa-miR-30d-5p,hsa-miR-30d-3p MIMAT0000245,MIMAT0004551 miRNA ATG2A autophagy down Homo sapiens epithelial cancer cells 23274497 9606 23130 - HGNC:29028|Ensembl:ENSG00000110046|HPRD:17186|Vega:OTTHUMG00000066831 11 11q13.1 autophagy related 2A protein-coding autophagy related 2A Using a combined bioinformatics approach, gene set enrichment analysis, and miRNA target prediction, we found that mir-30d might regulate multiple genes in the autophagy pathway including BECN1, BNIP3L, ATG12, ATG5, and ATG2. 208 mir-30d hsa-miR-30d-5p,hsa-miR-30d-3p MIMAT0000245,MIMAT0004551 miRNA ATG2B autophagy down Homo sapiens epithelial 23274497 9606 55102 C14orf103 HGNC:20187|Ensembl:ENSG00000066739|HPRD:12626|Vega:OTTHUMG00000149933 14 14q32.2 autophagy related 2B protein-coding autophagy related 2B Using a combined bioinformatics approach, gene set enrichment analysis, and miRNA target prediction, we found that mir-30d might regulate multiple genes in the autophagy pathway including BECN1, BNIP3L, ATG12, ATG5, and ATG2. 209 mir-30d hsa-miR-30d-5p,hsa-miR-30d-3p MIMAT0000245,MIMAT0004551 miRNA ATG5 autophagy down Homo sapiens epithelial 23274497 9606 9474 APG5|APG5-LIKE|APG5L|ASP|hAPG5 HGNC:589|MIM:604261|Ensembl:ENSG00000057663|HPRD:16051|Vega:OTTHUMG00000016193 6 6q21 autophagy related 5 protein-coding autophagy related 5 Using a combined bioinformatics approach, gene set enrichment analysis, and miRNA target prediction, we found that mir-30d might regulate multiple genes in the autophagy pathway including BECN1, BNIP3L, ATG12, ATG5, and ATG2. 210 mir-30d hsa-miR-30d-5p,hsa-miR-30d-3p MIMAT0000245,MIMAT0004551 miRNA BECN1 autophagy down Homo sapiens epithelial 23274497 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related Using a combined bioinformatics approach, gene set enrichment analysis, and miRNA target prediction, we found that mir-30d might regulate multiple genes in the autophagy pathway including BECN1, BNIP3L, ATG12, ATG5, and ATG2. 211 miR-30d hsa-miR-30d-5p,hsa-miR-30d-3p MIMAT0000245,MIMAT0004551 miRNA BECN1 autophagy down Homo sapiens anaplastic thyroid carcinoma 24345332 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related A reporter gene assay demonstrated that the binding sequences of miR-30d in the beclin 1-3' UTR was the region required for the inhibition of beclin 1 expression by this miRNA. 212 miR-30d hsa-miR-30d-5p,hsa-miR-30d-3p MIMAT0000245,MIMAT0004551 miRNA BNIP3L autophagy down Homo sapiens epithelial cancer cells 23274497 9606 665 BNIP3a|NIX HGNC:1085|MIM:605368|Ensembl:ENSG00000104765|HPRD:07288|Vega:OTTHUMG00000099433 8 8p21 BCL2/adenovirus E1B 19kDa interacting protein 3-like protein-coding BCL2/adenovirus E1B 19kDa interacting protein 3-like Using a combined bioinformatics approach, gene set enrichment analysis, and miRNA target prediction, we found that mir-30d might regulate multiple genes in the autophagy pathway including BECN1, BNIP3L, ATG12, ATG5, and ATG2. 213 miR-31 hsa-miR-31-5p,hsa-miR-31-3p MIMAT0000089,MIMAT0004504 miRNA GSK3B autophagy down Homo sapiens 24343269 9606 2932 - HGNC:4617|MIM:605004|Ensembl:ENSG00000082701|HPRD:05418|Vega:OTTHUMG00000133765 3 3q13.3 glycogen synthase kinase 3 beta protein-coding glycogen synthase kinase 3 beta Importantly, cellular levels of PP2A, a phosphatase, were regulated by Mir155 and Mir31 to fine-tune autophagy. Diminished expression of PP2A led to inhibition of GSK3B, thus facilitating the prolonged activation of WNT and SHH signaling pathways. Sustained WNT and SHH signaling effectuated the expression of anti-inflammatory lipoxygenases, which in tandem inhibited IFNG-induced JAK-STAT signaling and contributed to evasion of autophagy. 214 miR-31 hsa-miR-31-5p,hsa-miR-31-3p MIMAT0000089,MIMAT0004504 miRNA HIF1A autophagy up Homo sapiens 20861672 9606 3091 HIF-1A|HIF-1alpha|HIF1|HIF1-ALPHA|MOP1|PASD8|bHLHe78 HGNC:4910|MIM:603348|Ensembl:ENSG00000100644|HPRD:04517|Vega:OTTHUMG00000140344 14 14q23.2 hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) protein-coding hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) MiR-34c and miR-31 are associated with oxidative stress or activation of the hypoxic response/HIF1a, which is sufficient to drive authophagy/mitophagy. 215 miR-31 hsa-miR-31-5p,hsa-miR-31-3p MIMAT0000089,MIMAT0004504 miRNA PPP2R4 autophagy down Homo sapiens 24343269 9606 5524 PP2A|PR53|PTPA HGNC:9308|MIM:600756|Ensembl:ENSG00000119383|HPRD:02858|Vega:OTTHUMG00000020774 9 9q34 protein phosphatase 2A activator, regulatory subunit 4 protein-coding protein phosphatase 2A activator, regulatory subunit 4 Importantly, cellular levels of PP2A, a phosphatase, were regulated by Mir155 and Mir31 to fine-tune autophagy. Diminished expression of PP2A led to inhibition of GSK3B, thus facilitating the prolonged activation of WNT and SHH signaling pathways. Sustained WNT and SHH signaling effectuated the expression of anti-inflammatory lipoxygenases, which in tandem inhibited IFNG-induced JAK-STAT signaling and contributed to evasion of autophagy. 216 miR-31 hsa-miR-31-5p,hsa-miR-31-3p MIMAT0000089,MIMAT0004504 miRNA autophagy Homo sapiens 22342941 9606 In this review, we focus on highlighting the dual functions of miRNAs as either oncogenes (e.g., miRNA-183, miRNA-376b, miRNA-106a, miRNA-221/222, miRNA-31 and miRNA-34c) or tumor suppressors (e.g., miRNA-30a, miRNA-101 and miRNA-9*) via mediating several autophagic signaling pathways in cancer pathogenesis. Taken together, these findings may uncover the regulatory mechanisms of oncogenic and tumor suppressive miRNAs in autophagy, which would provide a better understanding of miRNA-modulated autophagic signaling networks for future cancer therapeutics. 217 miR-320a hsa-miR-320a MIMAT0000510 miRNA SNCA autophagy up Homo sapiens neuron 25207598 9606 6622 NACP|PARK1|PARK4|PD1 HGNC:11138|MIM:163890|Ensembl:ENSG00000145335|HPRD:01227 4 4q21 synuclein, alpha (non A4 component of amyloid precursor) protein-coding synuclein, alpha (non A4 component of amyloid precursor) Targeted suppression of chaperone-mediated autophagy by miR-320a promotes ¦Á-synuclein aggregation. 218 miR-34a hsa-miR-34a-5p,hsa-miR-34a-3p MIMAT0000255,MIMAT0004557 miRNA ATG9A autophagy down Homo sapiens 22902544 9606 79065 APG9L1|MGD3208|mATG9 HGNC:22408|MIM:612204|Ensembl:ENSG00000198925|HPRD:07979|Vega:OTTHUMG00000154557 2 2q35 autophagy related 9A protein-coding autophagy related 9A miR-34a, which besides its well-established effects related to cell-cycle arrest and senescence (39¨C41) has recently been identified as an inhibitor of autophagic flux and a direct regulator of ATG9A in mammalian cells 219 miR-34c hsa-miR-31-5p,hsa-miR-31-3p MIMAT0000089,MIMAT0004504 miRNA HIF1A autophagy up Homo sapiens caveolin-1(-/-) null stromal cells 20861672 9606 3091 HIF-1A|HIF-1alpha|HIF1|HIF1-ALPHA|MOP1|PASD8|bHLHe78 HGNC:4910|MIM:603348|Ensembl:ENSG00000100644|HPRD:04517|Vega:OTTHUMG00000140344 14 14q23.2 hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) protein-coding hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) MiR-34c and miR-31 are associated with oxidative stress or activation of the hypoxic response/HIF1a, which is sufficient to drive authophagy/mitophagy. 220 miR-34c hsa-miR-34c-5p,hsa-miR-34c-3p MIMAT0000686,MIMAT0004677 miRNA autophagy Homo sapiens 22342941 9606 In this review, we focus on highlighting the dual functions of miRNAs as either oncogenes (e.g., miRNA-183, miRNA-376b, miRNA-106a, miRNA-221/222, miRNA-31 and miRNA-34c) or tumor suppressors (e.g., miRNA-30a, miRNA-101 and miRNA-9*) via mediating several autophagic signaling pathways in cancer pathogenesis. Taken together, these findings may uncover the regulatory mechanisms of oncogenic and tumor suppressive miRNAs in autophagy, which would provide a better understanding of miRNA-modulated autophagic signaling networks for future cancer therapeutics. 221 miR-372 hsa-miR-372-3p,hsa-miR-372-5p MIMAT0000724,MIMAT0026484 miRNA SQSTM1 autophagy up Homo sapiens 24991827 9606 8878 A170|OSIL|PDB3|ZIP3|p60|p62|p62B HGNC:11280|MIM:601530|Ensembl:ENSG00000161011|HPRD:03319|Vega:OTTHUMG00000150643 5 5q35 sequestosome 1 protein-coding sequestosome 1 YY1 regulated SQSTM1 expression through the epigenetic modulation of the transcription of MIR372 (microRNA 372) which was found to target SQSTM1 directly. During nutrient starvation, YY1 was stimulated to promote SQSTM1 expression and subsequent autophagy activation by suppressing MIR372 expression. 222 miR-374a hsa-miR-374a-5p,hsa-miR-374a-3p MIMAT0004688,MIMAT0000727 miRNA ATG10 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 83734 APG10|APG10L|pp12616 HGNC:20315|MIM:610800|Ensembl:ENSG00000152348|HPRD:16497|Vega:OTTHUMG00000119041 5 5q14.1 autophagy related 10 protein-coding autophagy related 10 £¨We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. £©We identified APTs to directly interact with CD95 to promote de-palmitoylation, thus impairing apoptosis mediated through CD95. Specific inhibition of APTs by siRNAs, treatment with miRs-138/-424 and pharmacological approaches restore CD95-mediated apoptosis in CLL cells and other cancer cells, pointing to an important regulatory role of APTs in CD95 apoptosis. 223 miR-374a hsa-miR-374a-5p,hsa-miR-374a-3p MIMAT0000727,MIMAT0004688 miRNA ATG12 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 9140 APG12|APG12L|FBR93|HAPG12 HGNC:588|MIM:609608|Ensembl:ENSG00000145782|HPRD:08496|Vega:OTTHUMG00000128889 5 5q21-q22 autophagy related 12 protein-coding autophagy related 12 We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 224 miR-374a hsa-miR-374a-5p,hsa-miR-374a-3p MIMAT0000727,MIMAT0004688 miRNA ATG16L1 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 55054 APG16L|ATG16A|ATG16L|IBD10|WDR30 HGNC:21498|MIM:610767|Ensembl:ENSG00000085978|HPRD:16498|Vega:OTTHUMG00000133619 2 2q37.1 autophagy related 16-like 1 (S. cerevisiae) protein-coding autophagy related 16-like 1 (S. cerevisiae) We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 225 miR-374a hsa-miR-374a-5p,hsa-miR-374a-3p MIMAT0004688,MIMAT0000727 miRNA ATG5 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 9474 APG5|APG5-LIKE|APG5L|ASP|hAPG5 HGNC:589|MIM:604261|Ensembl:ENSG00000057663|HPRD:16051|Vega:OTTHUMG00000016193 6 6q21 autophagy related 5 protein-coding autophagy related 5 We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 226 miR-374a hsa-miR-374a-5p,hsa-miR-374a-3p MIMAT0000727,MIMAT0004688 miRNA ATG5 autophagy down Homo sapiens 22902544 9606 9474 APG5|APG5-LIKE|APG5L|ASP|hAPG5 HGNC:589|MIM:604261|Ensembl:ENSG00000057663|HPRD:16051|Vega:OTTHUMG00000016193 6 6q21 autophagy related 5 protein-coding autophagy related 5 ATG5-ATG12 forms a large multimeric complex with ATG16, which functions as the E3 ligase for LC3. Several miRNA regulators of this step have been identified including miR-30a, miR-181a and miR-374a (ATG5), miR-630 (ATG12), miR-376b (ATG4), miR-204 (LC3), miR-375 (ATG7), miR-519a (ATG10 and ATG16), miR-885-3p (ATG16) and miR-101 (ATG4 and RAB5A). 227 miR-374a hsa-miR-374a-5p,hsa-miR-374a-3p MIMAT0000727,MIMAT0004688 miRNA BECN1 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 228 miR-374a hsa-miR-374a-5p,hsa-miR-374a-3p MIMAT0000727,MIMAT0004688 miRNA TP63 autophagy down Homo sapiens squamous cell carcinoma cell 22356768 9606 8626 AIS|B(p51A)|B(p51B)|EEC3|KET|LMS|NBP|OFC8|RHS|SHFM4|TP53CP|TP53L|TP73L|p40|p51|p53CP|p63|p73H|p73L HGNC:15979|MIM:603273|Ensembl:ENSG00000073282|HPRD:04469|Vega:OTTHUMG00000156313 3 3q28 tumor protein p63 protein-coding tumor protein p63 We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 229 miR-374a hsa-miR-374a-5p,hsa-miR-374a-3p MIMAT0004688,MIMAT0000727 miRNA UVRAG autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 7405 DHTX|VPS38|p63 HGNC:12640|MIM:602493|HPRD:03929 11 11q13.5 UV radiation resistance associated protein-coding UV radiation resistance associated We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 230 miR-375 hsa-miR-375 MIMAT0000728 miRNA ATG7 autophagy down Homo sapiens hepatocellular carcinoma (HCC) cells 22504094 9606 10533 APG7-LIKE|APG7L|GSA7 HGNC:16935|MIM:608760|Ensembl:ENSG00000197548|HPRD:12293|Vega:OTTHUMG00000129740 3 3p25.3 autophagy related 7 protein-coding autophagy related 7 miR-375 inhibits autophagy by reducing expression of ATG7 and impairs viability of HCC cells under hypoxic conditions in culture and in mice. 231 miR-375 hsa-miR-375 MIMAT0000728 miRNA ATG7 autophagy down Homo sapiens hepatocellular carcinoma (HCC) cells 22902544 9606 10533 APG7-LIKE|APG7L|GSA7 HGNC:16935|MIM:608760|Ensembl:ENSG00000197548|HPRD:12293|Vega:OTTHUMG00000129740 3 3p25.3 autophagy related 7 protein-coding autophagy related 7 Although examples of inverse correlations between autophagy-regulating miRNAs and their targets in human cancers are emerging, including miR-375 and ATG7 in human HCC(33) and miR-204 and LC3B in RCC(27), little is known regarding the dynamics of the miRNA-autophagy interplay during tumor progression. 232 miR-375 hsa-miR-375 MIMAT0000728 miRNA ATG7 autophagy down Homo sapiens liver cancer cells 22929050 9606 10533 APG7-LIKE|APG7L|GSA7 HGNC:16935|MIM:608760|Ensembl:ENSG00000197548|HPRD:12293|Vega:OTTHUMG00000129740 3 3p25.3 autophagy related 7 protein-coding autophagy related 7 We found that MIR375 inhibited autophagosome formation, as indicated by the decreased number of green fluorescent protein (GFP)-LC3 puncta. In addition, both LC3-I and LC3-II detection and bafilomycin A1 assays supported that MIR375 blocked the conversion of LC3-I to LC3-II, which is required for the elongation of the phagopore and in turn, the formation of the autophagosome. 233 miR-375 hsa-miR-375 MIMAT0000728 miRNA ATG7 autophagy down Homo sapiens liver cancer cell 22929051 9606 10533 APG7-LIKE|APG7L|GSA7 HGNC:16935|MIM:608760|Ensembl:ENSG00000197548|HPRD:12293|Vega:OTTHUMG00000129740 3 3p25.3 autophagy related 7 protein-coding autophagy related 7 The suppression of ATG7 by MIR375 elucidated how MIR375 is able to block the conversion of LC3-I to LC3-II and thus to inhibit autophagy. 234 miR-375 hsa-miR-375 MIMAT0000728 miRNA MAP1LC3A autophagy down Homo sapiens liver cancer cell 22929050 9606 84557 ATG8E|LC3|LC3A|MAP1ALC3|MAP1BLC3 HGNC:6838|MIM:601242|Ensembl:ENSG00000101460|HPRD:03144|Vega:OTTHUMG00000032306 20 20q11.22 microtubule-associated protein 1 light chain 3 alpha protein-coding microtubule-associated protein 1 light chain 3 alpha We found that MIR375 inhibited autophagosome formation, as indicated by the decreased number of green fluorescent protein (GFP)-LC3 puncta. In addition, both LC3-I and LC3-II detection and bafilomycin A1 assays supported that MIR375 blocked the conversion of LC3-I to LC3-II, which is required for the elongation of the phagopore and in turn, the formation of the autophagosome. 235 miR-375 hsa-miR-375 MIMAT0000728 miRNA MAP1LC3B autophagy down Homo sapiens liver cancer cell 22929050 9606 81631 ATG8F|LC3B|MAP1A/1BLC3|MAP1LC3B-a HGNC:13352|MIM:609604|Ensembl:ENSG00000140941|HPRD:14358|Vega:OTTHUMG00000137654 16 16q24.2 microtubule-associated protein 1 light chain 3 beta protein-coding microtubule-associated protein 1 light chain 3 beta We found that MIR375 inhibited autophagosome formation, as indicated by the decreased number of green fluorescent protein (GFP)-LC3 puncta. In addition, both LC3-I and LC3-II detection and bafilomycin A1 assays supported that MIR375 blocked the conversion of LC3-I to LC3-II, which is required for the elongation of the phagopore and in turn, the formation of the autophagosome. 236 miR-375 hsa-miR-375 MIMAT0000728 miRNA SP1 autophagy down Homo sapiens K562 cell 22606351 9606 6667 - HGNC:11205|MIM:189906|Ensembl:ENSG00000185591|HPRD:01796|Vega:OTTHUMG00000170047 12 12q13.1 Sp1 transcription factor protein-coding Sp1 transcription factor This study has demonstrated that in the absence of p53 and p16, the induction of senescence by DOX was associated with upregulation of miR-375 and autophagy initiation. The anti-proliferative function of miR-375 is possibly exerted, at least in part, by targeting 14-3-3zeta and SP1 genes. 237 miR-375 hsa-miR-375 MIMAT0000728 miRNA YWHAZ autophagy down Homo sapiens K562 cell 22606351 9606 7534 14-3-3-zeta|HEL-S-3|HEL4|KCIP-1|YWHAD HGNC:12855|MIM:601288|Ensembl:ENSG00000164924|HPRD:03183|Vega:OTTHUMG00000134291 8 8q23.1 tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta protein-coding tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta This study has demonstrated that in the absence of p53 and p16, the induction of senescence by DOX was associated with upregulation of miR-375 and autophagy initiation. The anti-proliferative function of miR-375 is possibly exerted, at least in part, by targeting 14-3-3zeta and SP1 genes. 238 miR-376a hsa-miR-376a-2-5p,hsa-miR-376a-5p,hsa-miR-376a-3p MIMAT0000729,MIMAT0003386,MIMAT0022928 miRNA ATG4C autophagy down Homo sapiens MCF-7 and Huh7 cell 24358205 9606 84938 APG4-C|APG4C|AUTL1|AUTL3 HGNC:16040|MIM:611339|Ensembl:ENSG00000125703|HPRD:07473|Vega:OTTHUMG00000009142 1 1p31.3 autophagy related 4C, cysteine peptidase protein-coding autophagy related 4C, cysteine peptidase MIR376A is a regulator of starvation-induced autophagy.MIR376A shared the same seed sequence and had overlapping targets with MIR376B, and similarly blocked the expression of key autophagy proteins ATG4C and BECN1 (Beclin 1) 239 miR-376a hsa-miR-376a-2-5p,hsa-miR-376a-5p,hsa-miR-376a-3p MIMAT0000729,MIMAT0003386,MIMAT0022928 miRNA BECN1 autophagy down Homo sapiens MCF-7 and Huh7 cell 24358205 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related MIR376A is a regulator of starvation-induced autophagy.MIR376A shared the same seed sequence and had overlapping targets with MIR376B, and similarly blocked the expression of key autophagy proteins ATG4C and BECN1 (Beclin 1) 240 miR-376b hsa-miR-376b MIMAT0002172 miRNA ATG4C autophagy down Homo sapiens MCF-7 and Huh-7 cell 22248718 9606 84938 APG4-C|APG4C|AUTL1|AUTL3 HGNC:16040|MIM:611339|Ensembl:ENSG00000125703|HPRD:07473|Vega:OTTHUMG00000009142 1 1p31.3 autophagy related 4C, cysteine peptidase protein-coding autophagy related 4C, cysteine peptidase We discovered autophagy proteins ATG4C and BECN1 (Beclin 1) as cellular targets of miR-376b. Indeed, upon miRNA overexpression, both mRNA and protein levels of ATG4C and BECN1 were decreased. 241 miR-376b hsa-miR-376b MIMAT0002172 miRNA ATG4C autophagy down Homo sapiens 22902544 9606 84938 APG4-C|APG4C|AUTL1|AUTL3 HGNC:16040|MIM:611339|Ensembl:ENSG00000125703|HPRD:07473|Vega:OTTHUMG00000009142 1 1p31.3 autophagy related 4C, cysteine peptidase protein-coding autophagy related 4C, cysteine peptidase ATG5-ATG12 forms a large multimeric complex with ATG16, which functions as the E3 ligase for LC3. Several miRNA regulators of this step have been identified including miR-30a, miR-181a and miR-374a (ATG5), miR-630 (ATG12), miR-376b (ATG4), miR-204 (LC3), miR-375 (ATG7), miR-519a (ATG10 and ATG16), miR-885-3p (ATG16) and miR-101 (ATG4 and RAB5A). 242 miR-376b hsa-miR-376b MIMAT0002172 miRNA ATG4C autophagy down Homo sapiens MCF-7 and Huh7 cell 24358205 9606 84938 APG4-C|APG4C|AUTL1|AUTL3 HGNC:16040|MIM:611339|Ensembl:ENSG00000125703|HPRD:07473|Vega:OTTHUMG00000009142 1 1p31.3 autophagy related 4C, cysteine peptidase protein-coding autophagy related 4C, cysteine peptidase MIR376A is a regulator of starvation-induced autophagy.MIR376A shared the same seed sequence and had overlapping targets with MIR376B, and similarly blocked the expression of key autophagy proteins ATG4C and BECN1 (Beclin 1) 243 miR-376b hsa-miR-376b MIMAT0002172 miRNA BECN1 autophagy down Homo sapiens MCF-7 and Huh-7 cell 22248718 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related We discovered autophagy proteins ATG4C and BECN1 (Beclin 1) as cellular targets of miR-376b. Indeed, upon miRNA overexpression, both mRNA and protein levels of ATG4C and BECN1 were decreased. 244 miR-376b hsa-miR-376b MIMAT0002172 miRNA BECN1 autophagy down Homo sapiens breast cancer cells 22248719 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1. 245 miR-376b hsa-miR-376b MIMAT0002172 miRNA BECN1 autophagy down Homo sapiens 22902544 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related Vesicle nucleation mainly involves the Beclin-1 complex, which is positively or negatively regulated by a number of associated proteins. Beclin-1 itself is regulated by miR-30a, miR-376b and miR-519a. 246 miR-376b hsa-miR-376b MIMAT0002172 miRNA BECN1 autophagy down Homo sapiens MCF-7 and Huh7 cell 24358205 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related MIR376A is a regulator of starvation-induced autophagy.MIR376A shared the same seed sequence and had overlapping targets with MIR376B, and similarly blocked the expression of key autophagy proteins ATG4C and BECN1 (Beclin 1) 247 miR-376b hsa-miR-376b MIMAT0002172 miRNA autophagy Homo sapiens 22342941 9606 In this review, we focus on highlighting the dual functions of miRNAs as either oncogenes (e.g., miRNA-183, miRNA-376b, miRNA-106a, miRNA-221/222, miRNA-31 and miRNA-34c) or tumor suppressors (e.g., miRNA-30a, miRNA-101 and miRNA-9*) via mediating several autophagic signaling pathways in cancer pathogenesis. Taken together, these findings may uncover the regulatory mechanisms of oncogenic and tumor suppressive miRNAs in autophagy, which would provide a better understanding of miRNA-modulated autophagic signaling networks for future cancer therapeutics. 248 miR-4459 hsa-miR-4459 MIMAT0018981 miRNA ATG13 autophagy down Homo sapiens Embryonic Stem cell 25437332 9606 9776 KIAA0652|PARATARG8 HGNC:29091|MIM:615088|Ensembl:ENSG00000175224|HPRD:13809|Vega:OTTHUMG00000166538 11 11p11.2 autophagy related 13 protein-coding autophagy related 13 MiR-4459 could decrease the expression of its targets, CDC20B and ATG13, and thus altered stemness via cell cycle and autophagy. 249 miR-4459 hsa-miR-4459 MIMAT0018981 miRNA CDC20B autophagy down Homo sapiens Embryonic Stem cell 25437332 9606 166979 - HGNC:24222|Ensembl:ENSG00000164287|HPRD:13428|Vega:OTTHUMG00000131185 5 5q11.2 cell division cycle 20B protein-coding cell division cycle 20B MiR-4459 could decrease the expression of its targets, CDC20B and ATG13, and thus altered stemness via cell cycle and autophagy. 250 miR-4459 hsa-miR-4459 MIMAT0018981 miRNA TGFB2-OT1 autophagy Homo sapiens human umbilical vein endothelial cells 24879147 9606 103611157 HGNC:50629|Ensembl:ENSG00000281453 1 1q41 TGFB2 overlapping transcript 1 ncRNA TGFB2 overlapping transcript 1 In previous studies, we found a chemical small molecule, 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO), that inhibited autophagy in human umbilical vein endothelial cells (HUVECs) and neuronal cells.Finally, we used gene microarray, RNA interference, RNA-ChIP assay, bioinformatics, luciferase reporter assay, and other assays and found that 3BDO greatly decreased the level of a long noncoding RNA (lncRNA) derived from the 3' untranslated region (3'UTR) of TGFB2, known as FLJ11812.Further experiments results showed that FLJ11812 could bind with MIR4459 targeting ATG13 (autophagy-related 13), and ATG13 protein level was decreased along with 3BDO-decreased FLJ11812 level. 251 miR-451 hsa-miR-451a,hsa-miR-451b MIMAT0001631,MIMAT0019840 miRNA TSC1 autophagy down Homo sapiens HeLa cells 25209900 9606 7248 LAM|TSC HGNC:12362|MIM:605284|Ensembl:ENSG00000165699|HPRD:05594|Vega:OTTHUMG00000020844 9 9q34 tuberous sclerosis 1 protein-coding tuberous sclerosis 1 MiR-451 is decreased in hypertrophic cardiomyopathy and regulates autophagy by targeting TSC1. 252 miR-502 hsa-miR-502-5p,hsa-miR-502-3p MIMAT0002873,MIMAT0004775 miRNA RAB1B autophagy down Homo sapiens colon cancer cells 22580605 9606 81876 - HGNC:18370|MIM:612565|Ensembl:ENSG00000174903|HPRD:11469|Vega:OTTHUMG00000166916 11 11q12 RAB1B, member RAS oncogene family protein-coding RAB1B, member RAS oncogene family In this study, we discover a novel mechanism of autophagy regulated by hsa-miR-502-5p (miR-502) by suppression of Rab1B, a critical mediator of autophagy. 253 miR-519a hsa-miR-519a-3p,hsa-miR-519a-5p MIMAT0002869,MIMAT0005452 miRNA ATG10 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 83734 APG10|APG10L|pp12616 HGNC:20315|MIM:610800|Ensembl:ENSG00000152348|HPRD:16497|Vega:OTTHUMG00000119041 5 5q14.1 autophagy related 10 protein-coding autophagy related 10 £¨We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure.£©We identified APTs to directly interact with CD95 to promote de-palmitoylation, thus impairing apoptosis mediated through CD95. Specific inhibition of APTs by siRNAs, treatment with miRs-138/-424 and pharmacological approaches restore CD95-mediated apoptosis in CLL cells and other cancer cells, pointing to an important regulatory role of APTs in CD95 apoptosis. 254 miR-519a hsa-miR-519a-3p,hsa-miR-519a-5p MIMAT0002869,MIMAT0005452 miRNA ATG10 autophagy down Homo sapiens 22902544 9606 83734 APG10|APG10L|pp12616 HGNC:20315|MIM:610800|Ensembl:ENSG00000152348|HPRD:16497|Vega:OTTHUMG00000119041 5 5q14.1 autophagy related 10 protein-coding autophagy related 10 ATG5-ATG12 forms a large multimeric complex with ATG16, which functions as the E3 ligase for LC3. Several miRNA regulators of this step have been identified including miR-30a, miR-181a and miR-374a (ATG5), miR-630 (ATG12), miR-376b (ATG4), miR-204 (LC3), miR-375 (ATG7), miR-519a (ATG10 and ATG16), miR-885-3p (ATG16) and miR-101 (ATG4 and RAB5A). 255 miR-519a hsa-miR-519a-3p,hsa-miR-519a-5p MIMAT0002869,MIMAT0005452 miRNA ATG12 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 9140 APG12|APG12L|FBR93|HAPG12 HGNC:588|MIM:609608|Ensembl:ENSG00000145782|HPRD:08496|Vega:OTTHUMG00000128889 5 5q21-q22 autophagy related 12 protein-coding autophagy related 12 We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 256 miR-519a hsa-miR-519a-3p,hsa-miR-519a-5p MIMAT0002869,MIMAT0005452 miRNA ATG16L1 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 55054 APG16L|ATG16A|ATG16L|IBD10|WDR30 HGNC:21498|MIM:610767|Ensembl:ENSG00000085978|HPRD:16498|Vega:OTTHUMG00000133619 2 2q37.1 autophagy related 16-like 1 (S. cerevisiae) protein-coding autophagy related 16-like 1 (S. cerevisiae) We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 257 miR-519a hsa-miR-519a-3p,hsa-miR-519a-5p MIMAT0002869,MIMAT0005452 miRNA ATG16L1 autophagy down Homo sapiens 22902544 9606 55054 APG16L|ATG16A|ATG16L|IBD10|WDR30 HGNC:21498|MIM:610767|Ensembl:ENSG00000085978|HPRD:16498|Vega:OTTHUMG00000133619 2 2q37.1 autophagy related 16-like 1 (S. cerevisiae) protein-coding autophagy related 16-like 1 (S. cerevisiae) ATG5-ATG12 forms a large multimeric complex with ATG16, which functions as the E3 ligase for LC3. Several miRNA regulators of this step have been identified including miR-30a, miR-181a and miR-374a (ATG5), miR-630 (ATG12), miR-376b (ATG4), miR-204 (LC3), miR-375 (ATG7), miR-519a (ATG10 and ATG16), miR-885-3p (ATG16) and miR-101 (ATG4 and RAB5A). 258 miR-519a hsa-miR-519a-3p,hsa-miR-519a-5p MIMAT0002869,MIMAT0005452 miRNA ATG5 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 9474 APG5|APG5-LIKE|APG5L|ASP|hAPG5 HGNC:589|MIM:604261|Ensembl:ENSG00000057663|HPRD:16051|Vega:OTTHUMG00000016193 6 6q21 autophagy related 5 protein-coding autophagy related 5 We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 259 miR-519a hsa-miR-519a-3p,hsa-miR-519a-5p MIMAT0002869,MIMAT0005452 miRNA BECN1 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 260 miR-519a hsa-miR-519a-3p,hsa-miR-519a-5p MIMAT0002869,MIMAT0005452 miRNA BECN1 autophagy down Homo sapiens 22902544 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related Finally, miR-519a, which similarly to miR-30a was downregulated by cisplatin treatment, was also found to regulate BECN1 in a 3¡äUTR reporter¨Cbased assay and inhibition of this miRNA could mimic the effect of cisplatin treatment on the BECN1 3¡äUTR 261 miR-519a hsa-miR-519a-3p,hsa-miR-519a-5p MIMAT0002869,MIMAT0005452 miRNA TP63 autophagy down Homo sapiens squamous cell carcinoma cell 22356768 9606 8626 AIS|B(p51A)|B(p51B)|EEC3|KET|LMS|NBP|OFC8|RHS|SHFM4|TP53CP|TP53L|TP73L|p40|p51|p53CP|p63|p73H|p73L HGNC:15979|MIM:603273|Ensembl:ENSG00000073282|HPRD:04469|Vega:OTTHUMG00000156313 3 3q28 tumor protein p63 protein-coding tumor protein p63 We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 262 miR-519a hsa-miR-519a-3p,hsa-miR-519a-5p MIMAT0002869,MIMAT0005452 miRNA UVRAG autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 7405 DHTX|VPS38|p63 HGNC:12640|MIM:602493|HPRD:03929 11 11q13.5 UV radiation resistance associated protein-coding UV radiation resistance associated We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 263 miR-630 hsa-miR-630 MIMAT0003299 miRNA ATG10 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 83734 APG10|APG10L|pp12616 HGNC:20315|MIM:610800|Ensembl:ENSG00000152348|HPRD:16497|Vega:OTTHUMG00000119041 5 5q14.1 autophagy related 10 protein-coding autophagy related 10 We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 264 miR-630 hsa-miR-630 MIMAT0003299 miRNA ATG12 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 9140 APG12|APG12L|FBR93|HAPG12 HGNC:588|MIM:609608|Ensembl:ENSG00000145782|HPRD:08496|Vega:OTTHUMG00000128889 5 5q21-q22 autophagy related 12 protein-coding autophagy related 12 We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 265 miR-630 hsa-miR-630 MIMAT0003299 miRNA ATG12 autophagy down Homo sapiens 22902544 9606 9140 APG12|APG12L|FBR93|HAPG12 HGNC:588|MIM:609608|Ensembl:ENSG00000145782|HPRD:08496|Vega:OTTHUMG00000128889 5 5q21-q22 autophagy related 12 protein-coding autophagy related 12 Other potential regulators of ATG5-ATG12 conjugation include miR-30a, miR-181a, miR-374a and miR-630 266 miR-630 hsa-miR-630 MIMAT0003299 miRNA ATG16L1 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 55054 APG16L|ATG16A|ATG16L|IBD10|WDR30 HGNC:21498|MIM:610767|Ensembl:ENSG00000085978|HPRD:16498|Vega:OTTHUMG00000133619 2 2q37.1 autophagy related 16-like 1 (S. cerevisiae) protein-coding autophagy related 16-like 1 (S. cerevisiae) We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 267 miR-630 hsa-miR-630 MIMAT0003299 miRNA ATG5 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 9474 APG5|APG5-LIKE|APG5L|ASP|hAPG5 HGNC:589|MIM:604261|Ensembl:ENSG00000057663|HPRD:16051|Vega:OTTHUMG00000016193 6 6q21 autophagy related 5 protein-coding autophagy related 5 We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 268 miR-630 hsa-miR-630 MIMAT0003299 miRNA BECN1 autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 269 miR-630 hsa-miR-630 MIMAT0003299 miRNA TP63 autophagy down Homo sapiens squamous cell carcinoma cell 22356768 9606 8626 AIS|B(p51A)|B(p51B)|EEC3|KET|LMS|NBP|OFC8|RHS|SHFM4|TP53CP|TP53L|TP73L|p40|p51|p53CP|p63|p73H|p73L HGNC:15979|MIM:603273|Ensembl:ENSG00000073282|HPRD:04469|Vega:OTTHUMG00000156313 3 3q28 tumor protein p63 protein-coding tumor protein p63 We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 270 miR-630 hsa-miR-630 MIMAT0003299 miRNA UVRAG autophagy Homo sapiens squamous cell carcinoma cell 22356768 9606 7405 DHTX|VPS38|p63 HGNC:12640|MIM:602493|HPRD:03929 11 11q13.5 UV radiation resistance associated protein-coding UV radiation resistance associated We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-¦¤Np63¦Á, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. 271 miR-885-3p hsa-miR-885-3p MIMAT0004948 miRNA AKT1 autophagy up Homo sapiens squamous carcinoma cells 22071691 9606 207 AKT|CWS6|PKB|PKB-ALPHA|PRKBA|RAC|RAC-ALPHA HGNC:391|MIM:164730|Ensembl:ENSG00000142208|HPRD:01261|Vega:OTTHUMG00000170795 14 14q32.32 v-akt murine thymoma viral oncogene homolog 1 protein-coding v-akt murine thymoma viral oncogene homolog 1 PKB alpha|RAC-PK-alpha|RA The p-¦¤Np63¦Á-induced miR-885-3p functions as a critical regulator of MDM4, ATK1, BCL2, ATG16L2, ULK2, CASP2 and CASP3 mRNAs via pairing with their respective ¡°recognition¡± sequences. Altogether, our results support the notion that miR-885-3p might contribute in regulation of cell viability, apoptosis and/or autophagy in squamous cell carcinoma cells upon cisplatin exposure. 272 miR-885-3p hsa-miR-885-3p MIMAT0004948 miRNA ATG13 autophagy down Homo sapiens 22902544 9606 9776 KIAA0652|PARATARG8 HGNC:29091|MIM:615088|Ensembl:ENSG00000175224|HPRD:13809|Vega:OTTHUMG00000166538 11 11p11.2 autophagy related 13 protein-coding autophagy related 13 Interestingly, conserved, predicted binding sites for miR-885-3p exist in additional early autophagy-regulating genes, including the ULK-binding partner ATG13, as well as ATG9A and ATG2B, best known from yeast for their regulation of the retrieval step, where lipid and proteins are recruited to the phagophore assembly site (PAS) 273 miR-885-3p hsa-miR-885-3p MIMAT0004948 miRNA ATG16L2 autophagy up Homo sapiens squamous cell carcinoma cells 22071691 9606 89849 ATG16B|WDR80 HGNC:25464|Ensembl:ENSG00000168010|HPRD:10959|Vega:OTTHUMG00000167961 11 11q13.4 autophagy related 16-like 2 (S. cerevisiae) protein-coding autophagy related 16-like 2 (S. cerevisiae) The p-¦¤Np63¦Á-induced miR-885-3p functions as a critical regulator of MDM4, ATK1, BCL2, ATG16L2, ULK2, CASP2 and CASP3 mRNAs via pairing with their respective ¡°recognition¡± sequences. Altogether, our results support the notion that miR-885-3p might contribute in regulation of cell viability, apoptosis and/or autophagy in squamous cell carcinoma cells upon cisplatin exposure. 274 miR-885-3p hsa-miR-885-3p MIMAT0004948 miRNA ATG2B autophagy down Homo sapiens 22902544 9606 55102 C14orf103 HGNC:20187|Ensembl:ENSG00000066739|HPRD:12626|Vega:OTTHUMG00000149933 14 14q32.2 autophagy related 2B protein-coding autophagy related 2B Interestingly, conserved, predicted binding sites for miR-885-3p exist in additional early autophagy-regulating genes, including the ULK-binding partner ATG13, as well as ATG9A and ATG2B, best known from yeast for their regulation of the retrieval step, where lipid and proteins are recruited to the phagophore assembly site (PAS) 275 miR-885-3p hsa-miR-885-3p MIMAT0004948 miRNA ATG9A autophagy down Homo sapiens 22902544 9606 79065 APG9L1|MGD3208|mATG9 HGNC:22408|MIM:612204|Ensembl:ENSG00000198925|HPRD:07979|Vega:OTTHUMG00000154557 2 2q35 autophagy related 9A protein-coding autophagy related 9A Interestingly, conserved, predicted binding sites for miR-885-3p exist in additional early autophagy-regulating genes, including the ULK-binding partner ATG13, as well as ATG9A and ATG2B, best known from yeast for their regulation of the retrieval step, where lipid and proteins are recruited to the phagophore assembly site (PAS) 276 miR-885-3p hsa-miR-885-3p MIMAT0004948 miRNA MDM4 autophagy up Homo sapiens 22071691 9606 4194 HDMX|MDMX|MRP1 HGNC:6974|MIM:602704|Ensembl:ENSG00000198625|HPRD:04082|Vega:OTTHUMG00000035877 1 1q32 MDM4, p53 regulator protein-coding MDM4, p53 regulator The p-¦¤Np63¦Á-induced miR-885-3p functions as a critical regulator of MDM4, ATK1, BCL2, ATG16L2, ULK2, CASP2 and CASP3 mRNAs via pairing with their respective ¡°recognition¡± sequences. Altogether, our results support the notion that miR-885-3p might contribute in regulation of cell viability, apoptosis and/or autophagy in squamous cell carcinoma cells upon cisplatin exposure. 277 miR-885-3p hsa-miR-885-3p MIMAT0004948 miRNA ULK2 autophagy up Homo sapiens 22071691 9606 9706 ATG1B|Unc51.2 HGNC:13480|MIM:608650|Ensembl:ENSG00000083290|HPRD:10556|Vega:OTTHUMG00000059511 17 17p11.2 unc-51 like autophagy activating kinase 2 protein-coding unc-51 like autophagy activating kinase 2 The p-¦¤Np63¦Á-induced miR-885-3p functions as a critical regulator of MDM4, ATK1, BCL2, ATG16L2, ULK2, CASP2 and CASP3 mRNAs via pairing with their respective ¡°recognition¡± sequences. Altogether, our results support the notion that miR-885-3p might contribute in regulation of cell viability, apoptosis and/or autophagy in squamous cell carcinoma cells upon cisplatin exposure. 278 miR-9 hsa-miR-9-5p,hsa-miR-9-3p MIMAT0000441,MIMAT0000442 miRNA autophagy Homo sapiens 22342941 9606 In this review, we focus on highlighting the dual functions of miRNAs as either oncogenes (e.g., miRNA-183, miRNA-376b, miRNA-106a, miRNA-221/222, miRNA-31 and miRNA-34c) or tumor suppressors (e.g., miRNA-30a, miRNA-101 and miRNA-9*) via mediating several autophagic signaling pathways in cancer pathogenesis. Taken together, these findings may uncover the regulatory mechanisms of oncogenic and tumor suppressive miRNAs in autophagy, which would provide a better understanding of miRNA-modulated autophagic signaling networks for future cancer therapeutics. 279 miR-93 hsa-miR-93-5p,hsa-miR-93-3p MIMAT0000093,MIMAT0004509 miRNA ATG16L1 autophagy down Homo sapiens 24036151 9606 55054 APG16L|ATG16A|ATG16L|IBD10|WDR30 HGNC:21498|MIM:610767|Ensembl:ENSG00000085978|HPRD:16498|Vega:OTTHUMG00000133619 2 2q37.1 autophagy related 16-like 1 (S. cerevisiae) protein-coding autophagy related 16-like 1 (S. cerevisiae) Silencing Dicer1, an essential processor of miRs, increased levels of ATG protein and formation of autophagosomes in cells, indicating that miRs regulate autophagy. Luciferase reporter assays indicated that MIR106B and MIR93 targeted ATG16L1 messenger RNA. MIR106B and MIR93 reduced levels of ATG16L1 and autophagy; t 280 miR-93 hsa-miR-93-5p,hsa-miR-93-3p MIMAT0000093 ,MIMAT0004509 miRNA SQSTM1 autophagy up Homo sapiens myeloid 32D cells 22441107 9606 8878 A170|OSIL|PDB3|ZIP3|p60|p62|p62B HGNC:11280|MIM:601530|Ensembl:ENSG00000161011|HPRD:03319|Vega:OTTHUMG00000150643 5 5q35 sequestosome 1 protein-coding sequestosome 1 SQSTM1 (sequestosome 1/p62), a multiple domain protein that acts as a signaling hub, was identified as a key target for these miRNAs. SQSTM1 can interfere with autophagy via binding to the autophagic regulator Atg8/LC3. 281 miR-9-3p hsa-miR-9-3p MIMAT0000442 miRNA HDAC4 autophagy down Homo sapiens Waldenstrm macroglobulinemia (WM) cell 20519629 9606 9759 AHO3|BDMR|HA6116|HD4|HDAC-4|HDAC-A|HDACA HGNC:14063|MIM:605314|Ensembl:ENSG00000068024|HPRD:05610|Vega:OTTHUMG00000133344 2 2q37.3 histone deacetylase 4 protein-coding histone deacetylase 4 We found that restoring miRNA-9* levels induced toxicity in WM cells, supported by down-modulation of HDAC4 and HDAC5 and up-regulation of acetyl-histone-H3 and -H4. These, together with inhibited HDAC activity, led to induction of apoptosis and autophagy in WM cells. 282 miR-9-3p hsa-miR-9-3p MIMAT0000442 miRNA HDAC5 autophagy down Homo sapiens Waldenstrm macroglobulinemia (WM) cell 20519629 9606 10014 HD5|NY-CO-9 HGNC:14068|MIM:605315|Ensembl:ENSG00000108840|HPRD:09246|Vega:OTTHUMG00000181806 17 17q21 histone deacetylase 5 protein-coding histone deacetylase 5 We found that restoring miRNA-9* levels induced toxicity in WM cells, supported by down-modulation of HDAC4 and HDAC5 and up-regulation of acetyl-histone-H3 and -H4. These, together with inhibited HDAC activity, led to induction of apoptosis and autophagy in WM cells. 283 miR-9-3p hsa-miR-9-3p MIMAT0000442 miRNA HIST2H3C autophagy up Homo sapiens WM cell 20519629 9606 126961 H3|H3.2|H3/M|H3F2|H3FM|H3FN HGNC:20503|MIM:142780|HPRD:11822 1 1q21.2 histone cluster 2, H3c protein-coding histone cluster 2, H3c We found that restoring miRNA-9* levels induced toxicity in WM cells, supported by down-modulation of HDAC4 and HDAC5 and up-regulation of acetyl-histone-H3 and -H4. These, together with inhibited HDAC activity, led to induction of apoptosis and autophagy in WM cells. T 284 miR-9-3p hsa-miR-9-3p MIMAT0000442 miRNA HIST2H4A autophagy up Homo sapiens WM cell 20519629 9606 8370 FO108|H4|H4/n|H4F2|H4FN|HIST2H4 HGNC:4794|MIM:142750|Ensembl:ENSG00000183941|HPRD:11821|Vega:OTTHUMG00000012189 1 1q21.2 histone cluster 2, H4a protein-coding histone cluster 2, H4a We found that restoring miRNA-9* levels induced toxicity in WM cells, supported by down-modulation of HDAC4 and HDAC5 and up-regulation of acetyl-histone-H3 and -H4. These, together with inhibited HDAC activity, led to induction of apoptosis and autophagy in WM cells. T 285 miR-9-3p hsa-miR-9-3p MIMAT0000442 miRNA autophagy Homo sapiens 22342941 9606 In this review, we focus on highlighting the dual functions of miRNAs as either oncogenes (e.g., miRNA-183, miRNA-376b, miRNA-106a, miRNA-221/222, miRNA-31 and miRNA-34c) or tumor suppressors (e.g., miRNA-30a, miRNA-101 and miRNA-9*) via mediating several autophagic signaling pathways in cancer pathogenesis. Taken together, these findings may uncover the regulatory mechanisms of oncogenic and tumor suppressive miRNAs in autophagy, which would provide a better understanding of miRNA-modulated autophagic signaling networks for future cancer therapeutics. 286 miR-9-3p hsa-miR-9-3p MIMAT0000442 miRNA autophagy Homo sapiens SiHa cells 24944668 9606 miRNA-9* was also investigated. The results demonstrated that HCQ increased the expressions of LC3 mRNA and LC3II protein and GFP-LC3 signalling but reduced the expression of p62/STSQM1 in cervical cancer SiHa cells. These results indicated HCQ has the ability to inhibit autophagy as incapable of degrading the autophagosome. 287 miR-96 hsa-miR-96-5p,hsa-miR-96-3p MIMAT0000095,MIMAT0004510 miRNA ATG7 autophagy down Homo sapiens prostate cancer cells 25333253 9606 10533 APG7-LIKE|APG7L|GSA7 HGNC:16935|MIM:608760|Ensembl:ENSG00000197548|HPRD:12293|Vega:OTTHUMG00000129740 3 3p25.3 autophagy related 7 protein-coding autophagy related 7 Further studies have shown that high levels of miR-96 inhibited autophagy through suppressing ATG7, a key autophagy-associated gene. 288 miR-96 hsa-miR-96-5p,hsa-miR-96-3p MIMAT0000095,MIMAT0004510 miRNA MTOR autophagy down Homo sapiens prostate cancer cells 25333253 9606 2475 FRAP|FRAP1|FRAP2|RAFT1|RAPT1 HGNC:3942|MIM:601231|Ensembl:ENSG00000198793|HPRD:03134|Vega:OTTHUMG00000002001 1 1p36.2 mechanistic target of rapamycin (serine/threonine kinase) protein-coding mechanistic target of rapamycin (serine/threonine kinase) We report here hypoxia increased the expression of miR-96 in prostate cancer cells, and miR-96 stimulated autophagy by suppressing MTOR. 289 miR-96 hsa-miR-96-5p,hsa-miR-96-3p MIMAT0000095,MIMAT0004510 miRNA autophagy Homo sapiens 21293178 9606 MicroRNA enrichment analysis revealed miR-130, 98, 124, 204 and 142 as the putative post-transcriptional regulators of the autophagy-lysosomal pathway genes. 290 miR-98 hsa-miR-96-5p,hsa-miR-96-3p MIMAT0000095,MIMAT0004510 miRNA autophagy Homo sapiens 21293178 9606 MicroRNA enrichment analysis revealed miR-130, 98, 124, 204 and 142 as the putative post-transcriptional regulators of the autophagy-lysosomal pathway genes. 291 miR-UL148D(HCMV) hcmv-miR-UL148D MIMAT0001578 miRNA ERN1 autophagy Homo sapiens 24737391 9606 2081 IRE1|IRE1P|IRE1a|hIRE1p HGNC:3449|MIM:604033|Ensembl:ENSG00000178607|HPRD:04943|Vega:OTTHUMG00000178879 17 17q24.2 endoplasmic reticulum to nucleus signaling 1 protein-coding endoplasmic reticulum to nucleus signaling 1 The proapoptotic genes MOAP1, PHAP, and ERN1 are identified to be the potential targets for the miR-UL70-3p and UL148D, respectively. The ERN1 gene plays a role in the initiation of Endoplasmic reticulum stress-induced apoptosis as well as autophagosome formation. This study shows that HCMV employs its miRNA repertoire for countering the cellular apoptosis and autophagy, particularly the mitochondrial-dependent intrinsic pathway of apoptosis. 292 miR-UL70-3p(HCMV) hcmv-miR-UL70-3p MIMAT0003343 miRNA ERN1 autophagy Homo sapiens 24737391 9606 2081 IRE1|IRE1P|IRE1a|hIRE1p HGNC:3449|MIM:604033|Ensembl:ENSG00000178607|HPRD:04943|Vega:OTTHUMG00000178879 17 17q24.2 endoplasmic reticulum to nucleus signaling 1 protein-coding endoplasmic reticulum to nucleus signaling 1 The proapoptotic genes MOAP1, PHAP, and ERN1 are identified to be the potential targets for the miR-UL70-3p and UL148D, respectively. The ERN1 gene plays a role in the initiation of Endoplasmic reticulum stress-induced apoptosis as well as autophagosome formation. This study shows that HCMV employs its miRNA repertoire for countering the cellular apoptosis and autophagy, particularly the mitochondrial-dependent intrinsic pathway of apoptosis. 293 let-7b hsa-let-7b-5p,hsa-let-7b-3p MIMAT0000063,MIMAT0004482 miRNA ATG4B autophagy down Homo sapiens 22135297 9606 23192 APG4B|AUTL1 HGNC:20790|MIM:611338|Ensembl:ENSG00000168397|HPRD:16499|Vega:OTTHUMG00000151514 2 2q37.3 autophagy related 4B, cysteine peptidase protein-coding autophagy related 4B, cysteine peptidase This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 294 let-7i hsa-let-7i-5p,hsa-let-7i-3p MIMAT0000415,MIMAT0004585 miRNA IGF1R autophagy down Homo sapiens Jurkat cells 25305490 9606 3480 CD221|IGFIR|IGFR|JTK13 HGNC:5465|MIM:147370|Ensembl:ENSG00000140443|HPRD:00932|Vega:OTTHUMG00000149851 15 15q26.3 insulin-like growth factor 1 receptor protein-coding insulin-like growth factor 1 receptor Overexpression of let-7i inJurkat cells significantly suppressed IGF1R expression, which mimicked the actionof IGF1R siRNA. IGF1R inhibition led to a strinking decrease in phosphorylationof mTOR and Akt, down-regulation of Bcl-2, up-regulation of Bax and cleavage ofcaspase 3 and PARP. Meanwhile, IGF1R inhibition induced autophagy. 295 miR-100 hsa-miR-100-5p,hsa-miR-100-3p MIMAT0000098,MIMAT0004512 miRNA BECN1 autophagy down Homo sapiens 23622248 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 296 miR-101 hsa-miR-101-5p,hsa-miR-101-3p MIMAT0004513,MIMAT0000099 miRNA EZH2 autophagy up Homo sapiens HCC cell 24211739 9606 2146 ENX-1|ENX1|EZH1|EZH2b|KMT6|KMT6A|WVS|WVS2 HGNC:3527|MIM:601573|Ensembl:ENSG00000106462|HPRD:03342|Vega:OTTHUMG00000158973 7 7q35-q36 enhancer of zeste 2 polycomb repressive complex 2 subunit protein-coding enhancer of zeste 2 polycomb repressive complex 2 subunit MiR-101 expression was significantly downregulated in most of HCC tissues and all cell lines, whereas EZH2 was significantly overexpressed in most of HCC tissues and all cell lines. There was a negative correlation between expression levels of miR-101 and EZH2. Luciferase assay results confirmed EZH2 as a direct target gene of miR-101, which negatively regulates EZH2 expression in HCC. Ectopic overexpression of miR-101 dramatically repressed proliferation, invasion, colony formation as well as cell cycle progression in vitro and suppressed tumorigenicity in vivo. Furthermore, miR-101 inhibited autophagy and synergized with either doxorubicin or fluorouracil to induce apoptosis in tumor cells. 297 miR-101 hsa-miR-101-5p,hsa-miR-101-3p MIMAT0004513,MIMAT0000099 miRNA RAB5A autophagy Homo sapiens cardiomyocytes 25606826 9606 5868 RAB5 HGNC:9783|MIM:179512|Ensembl:ENSG00000144566|HPRD:01542|Vega:OTTHUMG00000129889 3 3p24-p22 RAB5A, member RAS oncogene family protein-coding RAB5A, member RAS oncogene family Further investigation identified Ras related protein Rab5A (RAB5A) as a direct target of miR-101. RAB5A was previously reported to be involved in autophagy; 298 miR-10a hsa-miR-10a-5p,hsa-miR-10a-3p MIMAT0000253,MIMAT0004555 miRNA ATG3 autophagy down Homo sapiens 23622248 9606 64422 APG3|APG3-LIKE|APG3L|PC3-96 HGNC:20962|MIM:609606|Ensembl:ENSG00000144848|HPRD:10654|Vega:OTTHUMG00000159260 3 3q13.2 autophagy related 3 protein-coding autophagy related 3 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 299 miR-1226 hsa-miR-1226-5p,hsa-miR-1226-3p MIMAT0005576,MIMAT0005577 miRNA PIK3R4 autophagy down Homo sapiens 23622248 9606 30849 VPS15|p150 HGNC:8982|MIM:602610|Ensembl:ENSG00000196455|HPRD:04010|Vega:OTTHUMG00000159645 3 3q22.1 phosphoinositide-3-kinase, regulatory subunit 4 protein-coding phosphoinositide-3-kinase, regulatory subunit 4 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 300 miR-124 hsa-miR-124-3p,hsa-miR-124-5p MIMAT0000422,MIMAT0004591 miRNA autophagy Homo sapiens colon cancer cell 25818238 9606 In this study, we investigated the role of miR-124 in colorectal adenoma (CRA) and cancer (CRC). The expression levels of miR-124 were decreased in CRA (81.8%) and CRC (57.6%) in 55 clinical samples. The ectopic expression of miR-124 induced apoptosis and autophagy in colon cancer cells. 301 miR-130b hsa-miR-130b-3p,hsa-miR-130b-5p MIMAT0000691,MIMAT0004680 miRNA FYCO1 autophagy down Homo sapiens 22135297 9606 79443 CATC2|CTRCT18|RUFY3|ZFYVE7 HGNC:14673|MIM:607182|Ensembl:ENSG00000163820|HPRD:06215|Vega:OTTHUMG00000133447 3 3p21.31 FYVE and coiled-coil domain containing 1 protein-coding FYVE and coiled-coil domain containing 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 302 miR-130b hsa-miR-130b-3p,hsa-miR-130b-5p MIMAT0000691,MIMAT0004680 miRNA UVRAG autophagy down Homo sapiens 22228303 9606 7405 DHTX|VPS38|p63 HGNC:12640|MIM:602493|HPRD:03929 11 11q13.5 UV radiation resistance associated protein-coding UV radiation resistance associated This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 303 miR-133b hsa-miR-130b-3p,hsa-miR-130b-5p MIMAT0000691,MIMAT0004680 miRNA RB1CC1 autophagy down Homo sapiens 23451058 9606 9821 ATG17|CC1|FIP200|PPP1R131 HGNC:15574|MIM:606837|Ensembl:ENSG00000023287|HPRD:06019|Vega:OTTHUMG00000164268 8 8q11 RB1-inducible coiled-coil 1 protein-coding RB1-inducible coiled-coil 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 304 miR-149 hsa-miR-149-5p,hsa-miR-149-3p MIMAT0000450,MIMAT0004609 miRNA PIK3C3 autophagy down Homo sapiens 23622248 9606 5289 VPS34|hVps34 HGNC:8974|MIM:602609|HPRD:04009 18 18q12.3 phosphatidylinositol 3-kinase, catalytic subunit type 3 protein-coding phosphatidylinositol 3-kinase, catalytic subunit type 3 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 305 miR-155 hsa-miR-155-5p,hsa-miR-155-3p MIMAT0000646,MIMAT0004658 miRNA ATG3 autophagy down Homo sapiens 22135297 9606 64422 APG3|APG3-LIKE|APG3L|PC3-96 HGNC:20962|MIM:609606|Ensembl:ENSG00000144848|HPRD:10654|Vega:OTTHUMG00000159260 3 3q13.2 autophagy related 3 protein-coding autophagy related 3 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 306 miR-155 hsa-miR-155-5p,hsa-miR-155-3p MIMAT0000646,MIMAT0004658 miRNA GABARAPL1 autophagy down Homo sapiens 20584899 9606 23710 APG8-LIKE|APG8L|ATG8|ATG8B|ATG8L|GEC1 HGNC:4068|MIM:607420|Ensembl:ENSG00000139112|HPRD:07601|Vega:OTTHUMG00000168411 12 12p13.2 GABA(A) receptor-associated protein like 1 protein-coding GABA(A) receptor-associated protein like 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 307 miR-155 hsa-miR-155-5p,hsa-miR-155-3p MIMAT0000646,MIMAT0004658 miRNA autophagy Homo sapiens osteosarcoma cell 25009614 9606 Our results demonstrated that microRNA-155 (miR-155) expression was highly induced during chemotherapy of osteosarcoma cells, and this was accompanied by upregulated autophagy. The increased miR-155 expression levels upregulated anticancer drug-induced autophagy in osteosarcoma cells and ameliorated the anticancer drug-induced cell proliferation and viability decrease. Therefore, the results of the present study demonstrated that miR-155 mediated drug-resistance in osteosarcoma cells by inducing autophagy. 308 miR-17 hsa-miR-17-5p,hsa-miR-17-3p MIMAT0000070,MIMAT0000071 miRNA BECN1 autophagy Homo sapiens lung cancer cells 25435430 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related MiR-17 overexpression reducedcytoprotective autophagy by targeting Beclin-1, whereas overexpression of miR-16 potentiated paclitaxel induced apoptotic cell death by inhibiting anti-apoptotic protein Bcl-2. 309 miR-17-5p hsa-miR-17-5p MIMAT0000070 miRNA BECN1 autophagy down Homo sapiens lung cancer cells A549 24755562 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related Overexpression of miR-17-5p into paclitaxel resistant lungcancer cells reduced beclin1 expression and a concordant decease in cellularautophagy. 310 miR-182 hsa-miR-182-5p,hsa-miR-182-3p MIMAT0000259,MIMAT0000260 miRNA ATG12 autophagy up Homo sapiens muscle cell 24871856 9606 9140 APG12|APG12L|FBR93|HAPG12 HGNC:588|MIM:609608|Ensembl:ENSG00000145782|HPRD:08496|Vega:OTTHUMG00000128889 5 5q21-q22 autophagy related 12 protein-coding autophagy related 12 Skeletal muscle atrophy occurs in response to a variety of conditions including chronic kidney disease, diabetes, cancer, and elevated glucocorticoids. MicroRNAs (miR) may play a role in the wasting process. Activation of the forkhead box O3 (FoxO3) transcription factor causes skeletal muscle atrophy in patients, animals, and cultured cells by increasing the expression of components of the ubiquitin-proteasome and autophagy-lysosome proteolytic systems. Transfection of miR-182 into muscle cells decreased FoxO3 mRNA 30% and FoxO3 protein 67% (P < 0.05) and also prevented a glucocorticoid-induced upregulation of multiple FoxO3 gene targets including MAFbx/atrogin-1, autophagy-related protein 12 (ATG12), cathepsin L, and microtubule-associated protein light chain 3 (LC3). 311 miR-182 hsa-miR-182-5p,hsa-miR-182-3p MIMAT0000259,MIMAT0000260 miRNA FOXO3 autophagy down Homo sapiens muscle cell 24871856 9606 2309 AF6q21|FKHRL1|FKHRL1P2|FOXO2|FOXO3A HGNC:3821|MIM:602681|Ensembl:ENSG00000118689|HPRD:04061|Vega:OTTHUMG00000015327 6 6q21 forkhead box O3 protein-coding forkhead box O3 Skeletal muscle atrophy occurs in response to a variety of conditions including chronic kidney disease, diabetes, cancer, and elevated glucocorticoids. MicroRNAs (miR) may play a role in the wasting process. Activation of the forkhead box O3 (FoxO3) transcription factor causes skeletal muscle atrophy in patients, animals, and cultured cells by increasing the expression of components of the ubiquitin-proteasome and autophagy-lysosome proteolytic systems. Transfection of miR-182 into muscle cells decreased FoxO3 mRNA 30% and FoxO3 protein 67% (P < 0.05) and also prevented a glucocorticoid-induced upregulation of multiple FoxO3 gene targets including MAFbx/atrogin-1, autophagy-related protein 12 (ATG12), cathepsin L, and microtubule-associated protein light chain 3 (LC3). 312 miR-183 hsa-miR-183-5p,hsa-miR-183-3p MIMAT0000261,MIMAT0004560 miRNA MAP1LC3B autophagy up Homo sapiens thyroid cell 21622722 9606 81631 ATG8F|LC3B|MAP1A/1BLC3|MAP1LC3B-a HGNC:13352|MIM:609604|Ensembl:ENSG00000140941|HPRD:14358|Vega:OTTHUMG00000137654 16 16q24.2 microtubule-associated protein 1 light chain 3 beta protein-coding microtubule-associated protein 1 light chain 3 beta Knock down of miR-183 expression in the TT cell line induced a significant decrease in the viable cell count and upregulation of the protein LC3B, which is associated with autophagy. 313 miR-186 hsa-miR-186-5p,hsa-miR-186-3p MIMAT0000456,MIMAT0004612 miRNA ULK1 autophagy down Homo sapiens 23622248 9606 8408 ATG1|ATG1A|UNC51|Unc51.1|hATG1 HGNC:12558|MIM:603168|Ensembl:ENSG00000177169|HPRD:11933|Vega:OTTHUMG00000168052 12 12q24.3 unc-51 like autophagy activating kinase 1 protein-coding unc-51 like autophagy activating kinase 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 314 miR-188 hsa-miR-188-5p,hsa-miR-188-3p MIMAT0000457,MIMAT0004613 miRNA ATG16L1 autophagy down Homo sapiens 23622248 9606 55054 APG16L|ATG16A|ATG16L|IBD10|WDR30 HGNC:21498|MIM:610767|Ensembl:ENSG00000085978|HPRD:16498|Vega:OTTHUMG00000133619 2 2q37.1 autophagy related 16-like 1 (S. cerevisiae) protein-coding autophagy related 16-like 1 (S. cerevisiae) This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 315 miR-18a hsa-miR-18a-5p,hsa-miR-18a-3p MIMAT0000072,MIMAT0002891 miRNA HNRNPA1 autophagy down Homo sapiens colon cancer cell 24166503 9606 3178 ALS19|ALS20|HNRPA1|HNRPA1L3|IBMPFD3|hnRNP A1|hnRNP-A1 HGNC:5031|MIM:164017|Ensembl:ENSG00000135486|HPRD:01242|Vega:OTTHUMG00000169702 12 12q13.1 heterogeneous nuclear ribonucleoprotein A1 protein-coding heterogeneous nuclear ribonucleoprotein A1 An immunocytochemical study of hnRNP A1 and LC3-II and the inhibition of autophagy by 3-methyladenine and ATG7, p62 and BAG3 siRNA showed that miR-18a and hnRNP A1 formed a complex that was degraded through the autophagolysosomal pathway. This is the first report showing a novel function of a miR in the autophagolysosomal degradation of an oncogenic protein resulting from the creation of a complex consisting of the miR and a RNA-binding protein, which suppressed cancer progression. 316 miR-192 hsa-miR-192-5p,hsa-miR-192-3p MIMAT0000222,MIMAT0004543 miRNA ATG10 autophagy down Homo sapiens 22135297 9606 83734 APG10|APG10L|pp12616 HGNC:20315|MIM:610800|Ensembl:ENSG00000152348|HPRD:16497|Vega:OTTHUMG00000119041 5 5q14.1 autophagy related 10 protein-coding autophagy related 10 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 317 miR-192 hsa-miR-192-5p,hsa-miR-192-3p MIMAT0000222,MIMAT0004543 miRNA ATG4A autophagy down Homo sapiens 19074876 9606 115201 APG4A|AUTL2 HGNC:16489|MIM:300663|Ensembl:ENSG00000101844|HPRD:06455|Vega:OTTHUMG00000022176 X Xq22.1-q22.3 autophagy related 4A, cysteine peptidase protein-coding autophagy related 4A, cysteine peptidase This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 318 miR-192 hsa-miR-192-5p,hsa-miR-192-3p MIMAT0000222,MIMAT0004543 miRNA MAP1LC3B autophagy down Homo sapiens 22135297 9606 81631 ATG8F|LC3B|MAP1A/1BLC3|MAP1LC3B-a HGNC:13352|MIM:609604|Ensembl:ENSG00000140941|HPRD:14358|Vega:OTTHUMG00000137654 16 16q24.2 microtubule-associated protein 1 light chain 3 beta protein-coding microtubule-associated protein 1 light chain 3 beta This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 319 miR-192 hsa-miR-192-5p,hsa-miR-192-3p MIMAT0000222,MIMAT0004543 miRNA PIK3R4 autophagy down Homo sapiens 16822819 9606 30849 VPS15|p150 HGNC:8982|MIM:602610|Ensembl:ENSG00000196455|HPRD:04010|Vega:OTTHUMG00000159645 3 3q22.1 phosphoinositide-3-kinase, regulatory subunit 4 protein-coding phosphoinositide-3-kinase, regulatory subunit 4 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 320 miR-192 hsa-miR-192-5p,hsa-miR-192-3p MIMAT0000222,MIMAT0004543 miRNA UVRAG autophagy down Homo sapiens 22135297 9606 7405 DHTX|VPS38|p63 HGNC:12640|MIM:602493|HPRD:03929 11 11q13.5 UV radiation resistance associated protein-coding UV radiation resistance associated This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 321 miR-193b hsa-miR-193b-5p,hsa-miR-193b-3p MIMAT0004767,MIMAT0002819 miRNA RB1CC1 autophagy down Homo sapiens 23622248 9606 9821 ATG17|CC1|FIP200|PPP1R131 HGNC:15574|MIM:606837|Ensembl:ENSG00000023287|HPRD:06019|Vega:OTTHUMG00000164268 8 8q11 RB1-inducible coiled-coil 1 protein-coding RB1-inducible coiled-coil 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 322 miR-193b hsa-miR-193b-5p,hsa-miR-193b-3p MIMAT0004767,MIMAT0002819 miRNA RB1CC1 autophagy down Homo sapiens 23622248 9606 9821 ATG17|CC1|FIP200|PPP1R131 HGNC:15574|MIM:606837|Ensembl:ENSG00000023287|HPRD:06019|Vega:OTTHUMG00000164268 8 8q11 RB1-inducible coiled-coil 1 protein-coding RB1-inducible coiled-coil 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 323 miR-200c hsa-miR-200c-3p,hsa-miR-200c-5p MIMAT0000617,MIMAT0004657 miRNA HMOX1 autophagy down Homo sapiens clear cell renal cell 25150313 9606 3162 HMOX1D|HO-1|HSP32|bK286B10 HGNC:5013|MIM:141250|Ensembl:ENSG00000100292|HPRD:00782|Vega:OTTHUMG00000150960 22 22q13.1 heme oxygenase (decycling) 1 protein-coding heme oxygenase (decycling) 1 Combined application with chemotherapeutic drugs, miR-200c, a?HO-1 inhibitor, may enhance the efficiency of therapy by promoting both apoptosis and autophagy. 324 miR-204 hsa-miR-204-5p,hsa-miR-204-3p MIMAT0000265,MIMAT0022693 miRNA MAP1LC3B autophagy down Homo sapiens renal clear cell 22516261 9606 81631 ATG8F|LC3B|MAP1A/1BLC3|MAP1LC3B-a HGNC:13352|MIM:609604|Ensembl:ENSG00000140941|HPRD:14358|Vega:OTTHUMG00000137654 16 16q24.2 microtubule-associated protein 1 light chain 3 beta protein-coding microtubule-associated protein 1 light chain 3 beta VHL-regulated miR-204 suppresses tumor growth through inhibition of LC3B-mediated autophagy in renal clear cell carcinoma. 325 miR-20a hsa-miR-20a-5p,hsa-miR-20a-3p MIMAT0000075,MIMAT0004493 miRNA ATG12 autophagy down Homo sapiens osteoclast 25485521 9606 9140 APG12|APG12L|FBR93|HAPG12 HGNC:588|MIM:609608|Ensembl:ENSG00000145782|HPRD:08496|Vega:OTTHUMG00000128889 5 5q21-q22 autophagy related 12 protein-coding autophagy related 12 Results of chromatin immunoprecipitation assay showed that HIF-1¦Á binds to miRNA-20a. From miRNA Q-PCR results, we confirmed that shRNA HIF-1¦Á knockdown significantly downregulated both autophagy (LC3, p62, Atg5, Atg12, Atg16l1, Atg7, Becn1, Atg9a) and osteoclast markers (Traf6, Nfatc1, Ctsk, cFos, Mmp9, Trap) in RAW264.7 cells. 326 miR-20a hsa-miR-20a-5p,hsa-miR-20a-3p MIMAT0000075,MIMAT0004493 miRNA ATG16L1 autophagy down Homo sapiens osteoclast 25485521 9606 55054 APG16L|ATG16A|ATG16L|IBD10|WDR30 HGNC:21498|MIM:610767|Ensembl:ENSG00000085978|HPRD:16498|Vega:OTTHUMG00000133619 2 2q37.1 autophagy related 16-like 1 (S. cerevisiae) protein-coding autophagy related 16-like 1 (S. cerevisiae) The results from dual luciferase reporter assay revealed that miR-20a directly targets Atg16l1 by binding to its 3'UTR end. Further, miR-20a transfection studies showed significant down regulation of autophagic proteins (LC3-II and ATG16L1) and osteoclast differentiation markers (Nfatc1, Traf6, and Trap) thus confirming the functional role of miR-20a under hypoxic conditions. Results of chromatin immunoprecipitation assay showed that HIF-1¦Á binds to miRNA-20a. From miRNA Q-PCR results, we confirmed that shRNA HIF-1¦Á knockdown significantly downregulated both autophagy (LC3, p62, Atg5, Atg12, Atg16l1, Atg7, Becn1, Atg9a) and osteoclast markers (Traf6, Nfatc1, Ctsk, cFos, Mmp9, Trap) in RAW264.7 cells. Thus, our findings suggest that the regulatory axis of HIF-1¦Á-miRNA-20a-Atg16l1 might be a critical mechanism for hypoxia-induced osteoclast differentiation. 327 miR-20a hsa-miR-20a-5p,hsa-miR-20a-3p MIMAT0000075,MIMAT0004493 miRNA ATG5 autophagy down Homo sapiens osteoclast 25485521 9606 9474 APG5|APG5-LIKE|APG5L|ASP|hAPG5 HGNC:589|MIM:604261|Ensembl:ENSG00000057663|HPRD:16051|Vega:OTTHUMG00000016193 6 6q21 autophagy related 5 protein-coding autophagy related 5 Results of chromatin immunoprecipitation assay showed that HIF-1¦Á binds to miRNA-20a. From miRNA Q-PCR results, we confirmed that shRNA HIF-1¦Á knockdown significantly downregulated both autophagy (LC3, p62, Atg5, Atg12, Atg16l1, Atg7, Becn1, Atg9a) and osteoclast markers (Traf6, Nfatc1, Ctsk, cFos, Mmp9, Trap) in RAW264.7 cells. 328 miR-20a hsa-miR-20a-5p,hsa-miR-20a-3p MIMAT0000075,MIMAT0004493 miRNA ATG7 autophagy down Homo sapiens osteoclast 25485521 9606 10533 APG7-LIKE|APG7L|GSA7 HGNC:16935|MIM:608760|Ensembl:ENSG00000197548|HPRD:12293|Vega:OTTHUMG00000129740 3 3p25.3 autophagy related 7 protein-coding autophagy related 7 Results of chromatin immunoprecipitation assay showed that HIF-1¦Á binds to miRNA-20a. From miRNA Q-PCR results, we confirmed that shRNA HIF-1¦Á knockdown significantly downregulated both autophagy (LC3, p62, Atg5, Atg12, Atg16l1, Atg7, Becn1, Atg9a) and osteoclast markers (Traf6, Nfatc1, Ctsk, cFos, Mmp9, Trap) in RAW264.7 cells. 329 miR-20a hsa-miR-20a-5p,hsa-miR-20a-3p MIMAT0000075,MIMAT0004493 miRNA ATG9A autophagy down Homo sapiens osteoclast 25485521 9606 79065 APG9L1|MGD3208|mATG9 HGNC:22408|MIM:612204|Ensembl:ENSG00000198925|HPRD:07979|Vega:OTTHUMG00000154557 2 2q35 autophagy related 9A protein-coding autophagy related 9A Results of chromatin immunoprecipitation assay showed that HIF-1¦Á binds to miRNA-20a. From miRNA Q-PCR results, we confirmed that shRNA HIF-1¦Á knockdown significantly downregulated both autophagy (LC3, p62, Atg5, Atg12, Atg16l1, Atg7, Becn1, Atg9a) and osteoclast markers (Traf6, Nfatc1, Ctsk, cFos, Mmp9, Trap) in RAW264.7 cells. 330 miR-20a hsa-miR-20a-5p,hsa-miR-20a-3p MIMAT0000075,MIMAT0004493 miRNA BECN1 autophagy down Homo sapiens osteoclast 25485521 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related Results of chromatin immunoprecipitation assay showed that HIF-1¦Á binds to miRNA-20a. From miRNA Q-PCR results, we confirmed that shRNA HIF-1¦Á knockdown significantly downregulated both autophagy (LC3, p62, Atg5, Atg12, Atg16l1, Atg7, Becn1, Atg9a) and osteoclast markers (Traf6, Nfatc1, Ctsk, cFos, Mmp9, Trap) in RAW264.7 cells. 331 miR-20a hsa-miR-20a-5p,hsa-miR-20a-3p MIMAT0000075,MIMAT0004493 miRNA HIF1A autophagy down Homo sapiens osteoclast 25485521 9606 3091 HIF-1A|HIF-1alpha|HIF1|HIF1-ALPHA|MOP1|PASD8|bHLHe78 HGNC:4910|MIM:603348|Ensembl:ENSG00000100644|HPRD:04517|Vega:OTTHUMG00000140344 14 14q23.2 hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) protein-coding hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) Results of chromatin immunoprecipitation assay showed that HIF-1¦Á binds to miRNA-20a. From miRNA Q-PCR results, we confirmed that shRNA HIF-1¦Á knockdown significantly downregulated both autophagy (LC3, p62, Atg5, Atg12, Atg16l1, Atg7, Becn1, Atg9a) and osteoclast markers (Traf6, Nfatc1, Ctsk, cFos, Mmp9, Trap) in RAW264.7 cells. 332 miR-20a hsa-miR-20a-5p,hsa-miR-20a-3p MIMAT0000075,MIMAT0004493 miRNA MAP1LC3B autophagy down Homo sapiens osteoclast 25485521 9606 81631 ATG8F|LC3B|MAP1A/1BLC3|MAP1LC3B-a HGNC:13352|MIM:609604|Ensembl:ENSG00000140941|HPRD:14358|Vega:OTTHUMG00000137654 16 16q24.2 microtubule-associated protein 1 light chain 3 beta protein-coding microtubule-associated protein 1 light chain 3 beta The results from dual luciferase reporter assay revealed that miR-20a directly targets Atg16l1 by binding to its 3'UTR end. Further, miR-20a transfection studies showed significant down regulation of autophagic proteins (LC3-II and ATG16L1) and osteoclast differentiation markers (Nfatc1, Traf6, and Trap) thus confirming the functional role of miR-20a under hypoxic conditions. Results of chromatin immunoprecipitation assay showed that HIF-1¦Á binds to miRNA-20a. From miRNA Q-PCR results, we confirmed that shRNA HIF-1¦Á knockdown significantly downregulated both autophagy (LC3, p62, Atg5, Atg12, Atg16l1, Atg7, Becn1, Atg9a) and osteoclast markers (Traf6, Nfatc1, Ctsk, cFos, Mmp9, Trap) in RAW264.7 cells. Thus, our findings suggest that the regulatory axis of HIF-1¦Á-miRNA-20a-Atg16l1 might be a critical mechanism for hypoxia-induced osteoclast differentiation. 333 miR-20a hsa-miR-20a-5p,hsa-miR-20a-3p MIMAT0000075,MIMAT0004493 miRNA SQSTM1 autophagy down Homo sapiens osteoclast 25485521 9606 8878 A170|OSIL|PDB3|ZIP3|p60|p62|p62B HGNC:11280|MIM:601530|Ensembl:ENSG00000161011|HPRD:03319|Vega:OTTHUMG00000150643 5 5q35 sequestosome 1 protein-coding sequestosome 1 Results of chromatin immunoprecipitation assay showed that HIF-1¦Á binds to miRNA-20a. From miRNA Q-PCR results, we confirmed that shRNA HIF-1¦Á knockdown significantly downregulated both autophagy (LC3, p62, Atg5, Atg12, Atg16l1, Atg7, Becn1, Atg9a) and osteoclast markers (Traf6, Nfatc1, Ctsk, cFos, Mmp9, Trap) in RAW264.7 cells. 334 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA BCL2 autophagy down Homo sapiens leukemia cells 23834154 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 MiR-21 downregulation also caused increased programmed cell death and a decrease in the expression levels of Bcl-2 protein, although PARP cleavage was not affected, indicating that apoptosis was not the relevant mechanism underlying the observed results. Treatment with antimiR-21 caused an increase in the autophagy related proteins Beclin-1, Vps34 and LC3-II. 335 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA BECN1 autophagy up Homo sapiens leukemia cells 23834154 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related MiR-21 downregulation also caused increased programmed cell death and a decrease in the expression levels of Bcl-2 protein, although PARP cleavage was not affected, indicating that apoptosis was not the relevant mechanism underlying the observed results. Treatment with antimiR-21 caused an increase in the autophagy related proteins Beclin-1, Vps34 and LC3-II. 336 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA MAP1LC3B autophagy up Homo sapiens leukemia cells 23834154 9606 81631 ATG8F|LC3B|MAP1A/1BLC3|MAP1LC3B-a HGNC:13352|MIM:609604|Ensembl:ENSG00000140941|HPRD:14358|Vega:OTTHUMG00000137654 16 16q24.2 microtubule-associated protein 1 light chain 3 beta protein-coding microtubule-associated protein 1 light chain 3 beta MiR-21 downregulation also caused increased programmed cell death and a decrease in the expression levels of Bcl-2 protein, although PARP cleavage was not affected, indicating that apoptosis was not the relevant mechanism underlying the observed results. Treatment with antimiR-21 caused an increase in the autophagy related proteins Beclin-1, Vps34 and LC3-II. 337 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PIK3C3 autophagy up Homo sapiens leukemia cells 23834154 9606 5289 VPS34|hVps34 HGNC:8974|MIM:602609|HPRD:04009 18 18q12.3 phosphatidylinositol 3-kinase, catalytic subunit type 3 protein-coding phosphatidylinositol 3-kinase, catalytic subunit type 3 MiR-21 downregulation also caused increased programmed cell death and a decrease in the expression levels of Bcl-2 protein, although PARP cleavage was not affected, indicating that apoptosis was not the relevant mechanism underlying the observed results. Treatment with antimiR-21 caused an increase in the autophagy related proteins Beclin-1, Vps34 and LC3-II. 338 miR-215 hsa-miR-192-5p,hsa-miR-192-3p MIMAT0000222,MIMAT0004543 miRNA ATG10 autophagy down Homo sapiens 19074876 9606 83734 APG10|APG10L|pp12616 HGNC:20315|MIM:610800|Ensembl:ENSG00000152348|HPRD:16497|Vega:OTTHUMG00000119041 5 5q14.1 autophagy related 10 protein-coding autophagy related 10 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 339 miR-215 hsa-miR-192-5p,hsa-miR-192-3p MIMAT0000222,MIMAT0004543 miRNA ATG10 autophagy down Homo sapiens 19074876 9606 83734 APG10|APG10L|pp12616 HGNC:20315|MIM:610800|Ensembl:ENSG00000152348|HPRD:16497|Vega:OTTHUMG00000119041 5 5q14.1 autophagy related 10 protein-coding autophagy related 10 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 340 miR-215 hsa-miR-192-5p,hsa-miR-192-3p MIMAT0000222,MIMAT0004543 miRNA ATG4A autophagy down Homo sapiens 19074876 9606 115201 APG4A|AUTL2 HGNC:16489|MIM:300663|Ensembl:ENSG00000101844|HPRD:06455|Vega:OTTHUMG00000022176 X Xq22.1-q22.3 autophagy related 4A, cysteine peptidase protein-coding autophagy related 4A, cysteine peptidase This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 341 miR-215 hsa-miR-192-5p,hsa-miR-192-3p MIMAT0000222,MIMAT0004543 miRNA ATG4A autophagy down Homo sapiens 19074876 9606 115201 APG4A|AUTL2 HGNC:16489|MIM:300663|Ensembl:ENSG00000101844|HPRD:06455|Vega:OTTHUMG00000022176 X Xq22.1-q22.3 autophagy related 4A, cysteine peptidase protein-coding autophagy related 4A, cysteine peptidase This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 342 miR-215 hsa-miR-192-5p,hsa-miR-192-3p MIMAT0000222,MIMAT0004543 miRNA UVRAG autophagy down Homo sapiens 19074876 9606 7405 DHTX|VPS38|p63 HGNC:12640|MIM:602493|HPRD:03929 11 11q13.5 UV radiation resistance associated protein-coding UV radiation resistance associated This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 343 miR-215 hsa-miR-192-5p,hsa-miR-192-3p MIMAT0000222,MIMAT0004543 miRNA UVRAG autophagy down Homo sapiens 19074876 9606 7405 DHTX|VPS38|p63 HGNC:12640|MIM:602493|HPRD:03929 11 11q13.5 UV radiation resistance associated protein-coding UV radiation resistance associated This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 344 miR-22 hsa-miR-22-5p,hsa-miR-22-3p MIMAT0004495,MIMAT0000077 miRNA BTG1 autophagy Homo sapiens CRC cells 25449431 9606 694 - HGNC:1130|MIM:109580|HPRD:15912 12 12q22 B-cell translocation gene 1, anti-proliferative protein-coding B-cell translocation gene 1, anti-proliferative B-cell translocationgene 1 (BTG1) was identified as a new target of miR-22, which could reverse theinhibition of autophagy induced by miR-22. 345 miR-23b hsa-miR-23b-3p,hsa-miR-23b-5p MIMAT0000418,MIMAT0004587 miRNA ROS1 autophagy Homo sapiens 24755453 9606 6098 MCF3|ROS|c-ros-1 HGNC:10261|MIM:165020|Ensembl:ENSG00000047936|HPRD:01295|Vega:OTTHUMG00000016188 6 6q22 ROS proto-oncogene 1 , receptor tyrosine kinase protein-coding ROS proto-oncogene 1 , receptor tyrosine kinase Among the wide family of microRNAs, microRNA 23b (miR-23b) intriguingly assumes opposite roles on regulation of reactive oxygen species (ROS) and on the development of human cancers. Finally, we analyze the involvement of miR-23b in cancer cell metabolism, including autophagy, and in biomarker signatures of microRNAs allowing a prognostic and therapeutic evaluation in various human cancers. 346 miR-25 hsa-miR-25-3p,hsa-miR-25-5p MIMAT0004498,MIMAT0000081 miRNA ULK1 autophagy up Homo sapiens breast cancer cells 25026296 9606 8408 ATG1|ATG1A|UNC51|Unc51.1|hATG1 HGNC:12558|MIM:603168|Ensembl:ENSG00000177169|HPRD:11933|Vega:OTTHUMG00000168052 12 12q24.3 unc-51 like autophagy activating kinase 1 protein-coding unc-51 like autophagy activating kinase 1 A mechanistic study validated that miR-25 inhibition led to autophagic cell death by directly increasing ULK1 expression,an early regulator in the autophagy induction phase. 347 miR-26b hsa-miR-26b-5p,hsa-miR-26b-3p MIMAT0004500,MIMAT0000083 miRNA GABARAP autophagy down Homo sapiens 22135297 9606 11337 ATG8A|GABARAP-a|MM46 HGNC:4067|MIM:605125|HPRD:05496 17 17p13.1 GABA(A) receptor-associated protein protein-coding GABA(A) receptor-associated protein This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 348 miR-26b hsa-miR-26b-5p,hsa-miR-26b-3p MIMAT0004500,MIMAT0000083 miRNA MAP1LC3C autophagy down Homo sapiens 19088304 9606 440738 ATG8J|LC3C HGNC:13353|MIM:609605|Ensembl:ENSG00000197769|HPRD:14226|Vega:OTTHUMG00000039865 1 1q43 microtubule-associated protein 1 light chain 3 gamma protein-coding microtubule-associated protein 1 light chain 3 gamma This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 349 miR-29b hsa-miR-29b-3p,hsa-miR-29b-1-5p,hsa-miR-29b-2-5p MIMAT0000100,MIMAT0004514,MIMAT0004515 miRNA PSME4 autophagy Homo sapiens 25234165 9606 23198 PA200 HGNC:20635|MIM:607705|Ensembl:ENSG00000068878|HPRD:09652|Vega:OTTHUMG00000151852 2 2p16.2 proteasome (prosome, macropain) activator subunit 4 protein-coding proteasome (prosome, macropain) activator subunit 4 Luciferase reporter assays demonstrated that miR-29b targeted PSME4 that encodes the proteasome activator PA200. Taken together, our study identifies miR-29b replacements as the first-in-class miR-based PIs that also disrupt the autophagy pathway and highlight their potential to synergistically enhance the antimyeloma effect of bortezomib. 350 miR-30a hsa-miR-30a-5p,hsa-miR-30a-3p MIMAT0000087,MIMAT0000088 miRNA BECN1 autophagy down Homo sapiens RCC cells 25712526 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related MiRNA-30a (miR-30a) is a potent inhibitor of autophagy by downregulating Beclin-1. 351 miR-30a hsa-miR-30a-5p,hsa-miR-30a-3p MIMAT0000087,MIMAT0000088 miRNA BECN1 autophagy up Homo sapiens neuroblastoma cells 24676932 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related To partly clarify this dualism, the effect of low-frequency EMF (LF-EMF) on the modulation of autophagy was investigated in human neuroblastoma SH-SY5Y cells, which were also subsequently exposed to A¦Â peptides, key players in AD. The results primarily point that LF-EMF induce a significant reduction of microRNA 30a (miR-30a) expression with a concomitant increase of Beclin1 transcript (BECN1) and its corresponding protein. Taking into account the pivotal role of autophagy in the clearance of protein aggregates within the cells, our results indicate a potential cytoprotective effect exerted by LF-EMF in neurodegenerative diseases such as AD. 352 miR-30a hsa-miR-30a-5p,hsa-miR-30a-3p MIMAT0000087,MIMAT0000088 miRNA GABARAPL2 autophagy down Homo sapiens 22135297 9606 11345 ATG8|ATG8C|GATE-16|GATE16|GEF-2|GEF2 HGNC:13291|MIM:607452|Ensembl:ENSG00000034713|HPRD:16246|Vega:OTTHUMG00000137613 16 16q22.1 GABA(A) receptor-associated protein-like 2 protein-coding GABA(A) receptor-associated protein-like 2 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 353 miR-30a hsa-miR-30a-5p,hsa-miR-30a-3p MIMAT0000087,MIMAT0000088 miRNA MAP1LC3B autophagy down Homo sapiens 22135297 9606 81631 ATG8F|LC3B|MAP1A/1BLC3|MAP1LC3B-a HGNC:13352|MIM:609604|Ensembl:ENSG00000140941|HPRD:14358|Vega:OTTHUMG00000137654 16 16q24.2 microtubule-associated protein 1 light chain 3 beta protein-coding microtubule-associated protein 1 light chain 3 beta This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 354 miR-30a hsa-miR-30a-5p,hsa-miR-30a-3p MIMAT0000087,MIMAT0000088 miRNA MAP1LC3B2 autophagy down Homo sapiens 18668040 9606 643246 ATG8G HGNC:34390|Ensembl:ENSG00000171471 12 12q24.22 microtubule-associated protein 1 light chain 3 beta 2 protein-coding microtubule-associated protein 1 light chain 3 beta 2 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 355 miR-32 hsa-miR-32-5p,hsa-miR-32-3p MIMAT0000090,MIMAT0004505 miRNA UVRAG autophagy down Homo sapiens 22135297 9606 7405 DHTX|VPS38|p63 HGNC:12640|MIM:602493|HPRD:03929 11 11q13.5 UV radiation resistance associated protein-coding UV radiation resistance associated This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 356 miR-320a hsa-miR-320a MIMAT0000510 miRNA ULK1 autophagy down Homo sapiens 23622248 9606 8408 ATG1|ATG1A|UNC51|Unc51.1|hATG1 HGNC:12558|MIM:603168|Ensembl:ENSG00000177169|HPRD:11933|Vega:OTTHUMG00000168052 12 12q24.3 unc-51 like autophagy activating kinase 1 protein-coding unc-51 like autophagy activating kinase 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 357 miR-330 hsa-miR-330-3p,hsa-miR-330-5p MIMAT0000751,MIMAT0004693 miRNA PIK3R4 autophagy down Homo sapiens 23622248 9606 30849 VPS15|p150 HGNC:8982|MIM:602610|Ensembl:ENSG00000196455|HPRD:04010|Vega:OTTHUMG00000159645 3 3q22.1 phosphoinositide-3-kinase, regulatory subunit 4 protein-coding phosphoinositide-3-kinase, regulatory subunit 4 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 358 miR-335 hsa-miR-335-5p,hsa-miR-335-3p MIMAT0000765,MIMAT0004703 miRNA ATG16L2 autophagy down Homo sapiens 18185580 9606 89849 ATG16B|WDR80 HGNC:25464|Ensembl:ENSG00000168010|HPRD:10959|Vega:OTTHUMG00000167961 11 11q13.4 autophagy related 16-like 2 (S. cerevisiae) protein-coding autophagy related 16-like 2 (S. cerevisiae) This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 359 miR-335 hsa-miR-335-5p,hsa-miR-335-3p MIMAT0000765,MIMAT0004703 miRNA GABARAPL1 autophagy down Homo sapiens 18185580 9606 23710 APG8-LIKE|APG8L|ATG8|ATG8B|ATG8L|GEC1 HGNC:4068|MIM:607420|Ensembl:ENSG00000139112|HPRD:07601|Vega:OTTHUMG00000168411 12 12p13.2 GABA(A) receptor-associated protein like 1 protein-coding GABA(A) receptor-associated protein like 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 360 miR-335 hsa-miR-335-5p,hsa-miR-335-3p MIMAT0000765,MIMAT0004703 miRNA MAP1LC3A autophagy down Homo sapiens 18185580 9606 84557 ATG8E|LC3|LC3A|MAP1ALC3|MAP1BLC3 HGNC:6838|MIM:601242|Ensembl:ENSG00000101460|HPRD:03144|Vega:OTTHUMG00000032306 20 20q11.22 microtubule-associated protein 1 light chain 3 alpha protein-coding microtubule-associated protein 1 light chain 3 alpha This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 361 miR-335 hsa-miR-335-5p,hsa-miR-335-3p MIMAT0000765,MIMAT0004703 miRNA MAP1LC3B autophagy down Homo sapiens 22135297 9606 81631 ATG8F|LC3B|MAP1A/1BLC3|MAP1LC3B-a HGNC:13352|MIM:609604|Ensembl:ENSG00000140941|HPRD:14358|Vega:OTTHUMG00000137654 16 16q24.2 microtubule-associated protein 1 light chain 3 beta protein-coding microtubule-associated protein 1 light chain 3 beta This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 362 miR-335 hsa-miR-335-5p,hsa-miR-335-3p MIMAT0000765,MIMAT0004703 miRNA SQSTM1 autophagy down Homo sapiens 22135297 9606 8878 A170|OSIL|PDB3|ZIP3|p60|p62|p62B HGNC:11280|MIM:601530|Ensembl:ENSG00000161011|HPRD:03319|Vega:OTTHUMG00000150643 5 5q35 sequestosome 1 protein-coding sequestosome 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 363 miR-335 hsa-miR-335-5p,hsa-miR-335-3p MIMAT0000765,MIMAT0004703 miRNA TECPR1 autophagy down Homo sapiens 22135297 9606 25851 - HGNC:22214|MIM:614781|Ensembl:ENSG00000205356|HPRD:08521|Vega:OTTHUMG00000154273 7 7q21.3 tectonin beta-propeller repeat containing 1 protein-coding tectonin beta-propeller repeat containing 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 364 miR-335 hsa-miR-335-5p,hsa-miR-335-3p MIMAT0000765,MIMAT0004703 miRNA ULK1 autophagy down Homo sapiens 22135297 9606 8408 ATG1|ATG1A|UNC51|Unc51.1|hATG1 HGNC:12558|MIM:603168|Ensembl:ENSG00000177169|HPRD:11933|Vega:OTTHUMG00000168052 12 12q24.3 unc-51 like autophagy activating kinase 1 protein-coding unc-51 like autophagy activating kinase 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 365 miR-335 hsa-miR-335-5p,hsa-miR-335-3p MIMAT0000765,MIMAT0004703 miRNA ULK2 autophagy down Homo sapiens 18185580 9606 9706 ATG1B|Unc51.2 HGNC:13480|MIM:608650|Ensembl:ENSG00000083290|HPRD:10556|Vega:OTTHUMG00000059511 17 17p11.2 unc-51 like autophagy activating kinase 2 protein-coding unc-51 like autophagy activating kinase 2 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 366 miR-34a hsa-miR-34a-5p,hsa-miR-34a-3p MIMAT0000255,MIMAT0004557 miRNA ATG4B autophagy down Homo sapiens chronic myeloid leukemia 24755409 9606 23192 APG4B|AUTL1 HGNC:20790|MIM:611338|Ensembl:ENSG00000168397|HPRD:16499|Vega:OTTHUMG00000151514 2 2q37.3 autophagy related 4B, cysteine peptidase protein-coding autophagy related 4B, cysteine peptidase Moreover, deregulated expression of ATG4B in CD34(+) CML cells inversely correlates with transcript levels of miR-34a, and ATG4B is shown to be a direct target of miR-34a. This study identifies ATG4B as a potential biomarker for predicting therapeutic response in treatment-na?ve CML stem/progenitor cells and uncovers ATG4B as a possible drug target in these cells. 367 miR-373 hsa-miR-373-5p,hsa-miR-373-3p MIMAT0000725,MIMAT0000726 miRNA FYCO1 autophagy down Homo sapiens 22135297 9606 79443 CATC2|CTRCT18|RUFY3|ZFYVE7 HGNC:14673|MIM:607182|Ensembl:ENSG00000163820|HPRD:06215|Vega:OTTHUMG00000133447 3 3p21.31 FYVE and coiled-coil domain containing 1 protein-coding FYVE and coiled-coil domain containing 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 368 miR-374b hsa-miR-374b-5p,hsa-miR-374b-3p MIMAT0004955,MIMAT0004956 miRNA GABARAPL1 autophagy down Homo sapiens 20371350 9606 23710 APG8-LIKE|APG8L|ATG8|ATG8B|ATG8L|GEC1 HGNC:4068|MIM:607420|Ensembl:ENSG00000139112|HPRD:07601|Vega:OTTHUMG00000168411 12 12p13.2 GABA(A) receptor-associated protein like 1 protein-coding GABA(A) receptor-associated protein like 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 369 miR-374b hsa-miR-374b-5p,hsa-miR-374b-3p MIMAT0004955,MIMAT0004956 miRNA GABARAPL1 autophagy down Homo sapiens 20371350 9606 23710 APG8-LIKE|APG8L|ATG8|ATG8B|ATG8L|GEC1 HGNC:4068|MIM:607420|Ensembl:ENSG00000139112|HPRD:07601|Vega:OTTHUMG00000168411 12 12p13.2 GABA(A) receptor-associated protein like 1 protein-coding GABA(A) receptor-associated protein like 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 370 miR-375 hsa-miR-375 MIMAT0000728 miRNA ATG7 autophagy down Homo sapiens 22135297 9606 10533 APG7-LIKE|APG7L|GSA7 HGNC:16935|MIM:608760|Ensembl:ENSG00000197548|HPRD:12293|Vega:OTTHUMG00000129740 3 3p25.3 autophagy related 7 protein-coding autophagy related 7 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 371 miR-375 hsa-miR-375 MIMAT0000728 miRNA RB1CC1 autophagy down Homo sapiens 22135297 9606 9821 ATG17|CC1|FIP200|PPP1R131 HGNC:15574|MIM:606837|Ensembl:ENSG00000023287|HPRD:06019|Vega:OTTHUMG00000164268 8 8q11 RB1-inducible coiled-coil 1 protein-coding RB1-inducible coiled-coil 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 372 miR-378a hsa-miR-378a-5p,hsa-miR-378a-3p MIMAT0000731,MIMAT0000732 miRNA FYCO1 autophagy down Homo sapiens 23622248 9606 79443 CATC2|CTRCT18|RUFY3|ZFYVE7 HGNC:14673|MIM:607182|Ensembl:ENSG00000163820|HPRD:06215|Vega:OTTHUMG00000133447 3 3p21.31 FYVE and coiled-coil domain containing 1 protein-coding FYVE and coiled-coil domain containing 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 373 miR-421 hsa-miR-421 MIMAT0003339 miRNA ATG2B autophagy down Homo sapiens 20371350 9606 55102 C14orf103 HGNC:20187|Ensembl:ENSG00000066739|HPRD:12626|Vega:OTTHUMG00000149933 14 14q32.2 autophagy related 2B protein-coding autophagy related 2B This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 374 miR-423 hsa-miR-423-5p,hsa-miR-423-3p MIMAT0004748,MIMAT0001340 miRNA SQSTM1 autophagy down Homo sapiens 23622248 9606 8878 A170|OSIL|PDB3|ZIP3|p60|p62|p62B HGNC:11280|MIM:601530|Ensembl:ENSG00000161011|HPRD:03319|Vega:OTTHUMG00000150643 5 5q35 sequestosome 1 protein-coding sequestosome 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 375 miR-423 hsa-miR-423-5p,hsa-miR-423-3p MIMAT0004748,MIMAT0001340 miRNA ULK1 autophagy down Homo sapiens 23622248 9606 8408 ATG1|ATG1A|UNC51|Unc51.1|hATG1 HGNC:12558|MIM:603168|Ensembl:ENSG00000177169|HPRD:11933|Vega:OTTHUMG00000168052 12 12q24.3 unc-51 like autophagy activating kinase 1 protein-coding unc-51 like autophagy activating kinase 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 376 miR-423-5p hsa-miR-423-5p MIMAT0004748 miRNA autophagy Homo sapiens hepatocellular carcinoma cell 25782064 9606 MiR-423-5p was validated as positive regulator of autophagy in HCC cell lines by transient transfection of miR and anti-miR molecules. 377 miR-484 hsa-miR-484 MIMAT0002174 miRNA FYCO1 autophagy down Homo sapiens 23622248 9606 79443 CATC2|CTRCT18|RUFY3|ZFYVE7 HGNC:14673|MIM:607182|Ensembl:ENSG00000163820|HPRD:06215|Vega:OTTHUMG00000133447 3 3p21.31 FYVE and coiled-coil domain containing 1 protein-coding FYVE and coiled-coil domain containing 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 378 miR-484 hsa-miR-484 MIMAT0002174 miRNA SQSTM1 autophagy down Homo sapiens 23622248 9606 8878 A170|OSIL|PDB3|ZIP3|p60|p62|p62B HGNC:11280|MIM:601530|Ensembl:ENSG00000161011|HPRD:03319|Vega:OTTHUMG00000150643 5 5q35 sequestosome 1 protein-coding sequestosome 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 379 miR-503 hsa-miR-503-5p,hsa-miR-503-3p MIMAT0022925,MIMAT0002874 miRNA PIK3R4 autophagy down Homo sapiens 23622248 9606 30849 VPS15|p150 HGNC:8982|MIM:602610|Ensembl:ENSG00000196455|HPRD:04010|Vega:OTTHUMG00000159645 3 3q22.1 phosphoinositide-3-kinase, regulatory subunit 4 protein-coding phosphoinositide-3-kinase, regulatory subunit 4 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 380 miR-503 hsa-miR-503-5p,hsa-miR-503-3p MIMAT0022925,MIMAT0002874 miRNA PIK3R4 autophagy down Homo sapiens 23622248 9606 30849 VPS15|p150 HGNC:8982|MIM:602610|Ensembl:ENSG00000196455|HPRD:04010|Vega:OTTHUMG00000159645 3 3q22.1 phosphoinositide-3-kinase, regulatory subunit 4 protein-coding phosphoinositide-3-kinase, regulatory subunit 4 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 381 miR-615 hsa-miR-615-5p,hsa-miR-615-3p MIMAT0004804,MIMAT0003283 miRNA FYCO1 autophagy down Homo sapiens 23622248 9606 79443 CATC2|CTRCT18|RUFY3|ZFYVE7 HGNC:14673|MIM:607182|Ensembl:ENSG00000163820|HPRD:06215|Vega:OTTHUMG00000133447 3 3p21.31 FYVE and coiled-coil domain containing 1 protein-coding FYVE and coiled-coil domain containing 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 382 miR-615 hsa-miR-615-5p,hsa-miR-615-3p MIMAT0004804,MIMAT0003283 miRNA FYCO1 autophagy down Homo sapiens 23622248 9606 79443 CATC2|CTRCT18|RUFY3|ZFYVE7 HGNC:14673|MIM:607182|Ensembl:ENSG00000163820|HPRD:06215|Vega:OTTHUMG00000133447 3 3p21.31 FYVE and coiled-coil domain containing 1 protein-coding FYVE and coiled-coil domain containing 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 383 miR-615 hsa-miR-615-5p,hsa-miR-615-3p MIMAT0004804,MIMAT0003283 miRNA UVRAG autophagy down Homo sapiens 23622248 9606 7405 DHTX|VPS38|p63 HGNC:12640|MIM:602493|HPRD:03929 11 11q13.5 UV radiation resistance associated protein-coding UV radiation resistance associated This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 384 miR-615 hsa-miR-615-5p,hsa-miR-615-3p MIMAT0004804,MIMAT0003283 miRNA UVRAG autophagy down Homo sapiens 23622248 9606 7405 DHTX|VPS38|p63 HGNC:12640|MIM:602493|HPRD:03929 11 11q13.5 UV radiation resistance associated protein-coding UV radiation resistance associated This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 385 miR-7 hsa-miR-7-5p,hsa-miR-7-1-3p,hsa-miR-7-2-3p MIMAT0000252,MIMAT0004553,MIMAT0004554 miRNA EGFR autophagy down Homo sapiens 22492316 9606 1956 ERBB|ERBB1|HER1|PIG61|mENA HGNC:3236|MIM:131550|Ensembl:ENSG00000146648|HPRD:00579|Vega:OTTHUMG00000023661 7 7p12 epidermal growth factor receptor protein-coding epidermal growth factor receptor Virus-mediated miR-7 upregulation depended on enhanced expression of the E2F1 protein. Ectopic expression of miR-7 suppressed cell viability and induced autophagy by inhibiting epidermal growth factor receptor (EGFR) expression. Our results suggest that oncolytic adenovirus induces autophagic cell death through an E2F1-miR-7-EGFR pathway in human cancer cells, providing a novel insight into the molecular mechanism of an anticancer virotherapy. 386 miR-877 hsa-miR-877-5p,hsa-miR-877-3p MIMAT0004949,MIMAT0004950 miRNA ATG4A autophagy down Homo sapiens 23622248 9606 115201 APG4A|AUTL2 HGNC:16489|MIM:300663|Ensembl:ENSG00000101844|HPRD:06455|Vega:OTTHUMG00000022176 X Xq22.1-q22.3 autophagy related 4A, cysteine peptidase protein-coding autophagy related 4A, cysteine peptidase This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 387 miR-877 hsa-miR-877-5p,hsa-miR-877-3p MIMAT0004949,MIMAT0004950 miRNA SQSTM1 autophagy down Homo sapiens 23622248 9606 8878 A170|OSIL|PDB3|ZIP3|p60|p62|p62B HGNC:11280|MIM:601530|Ensembl:ENSG00000161011|HPRD:03319|Vega:OTTHUMG00000150643 5 5q35 sequestosome 1 protein-coding sequestosome 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 388 miR-93 hsa-miR-93-5p,hsa-miR-93-3p MIMAT0000093,MIMAT0004509 miRNA FYCO1 autophagy down Homo sapiens 22135297 9606 79443 CATC2|CTRCT18|RUFY3|ZFYVE7 HGNC:14673|MIM:607182|Ensembl:ENSG00000163820|HPRD:06215|Vega:OTTHUMG00000133447 3 3p21.31 FYVE and coiled-coil domain containing 1 protein-coding FYVE and coiled-coil domain containing 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 389 miR-9-3p hsa-miR-9-3p MIMAT0000442 miRNA BECN1 autophagy up Homo sapiens medullary thyroid carcinoma cell 25487826 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related Post-miR-9-3p transfection array studies showed a significant global decline in autophagy gene expression (most notably in PIK3C3, mTOR, and LAMP-1). Autophagy gene mRNAs were generally overexpressed in sporadic (vs. hereditary MTC) and Beclin-1 overexpression was shown to correlate with residual disease. Autophagy is a tumor cell survival mechanism in MTC that when disabled, is of therapeutic advantage. Beclin-1 expression may be a useful prognostic biomarker of aggressive disease. 390 miR-9-3p hsa-miR-9-3p MIMAT0000442 miRNA LAMP1 autophagy down Homo sapiens medullary thyroid carcinoma cell 25487826 9606 3916 CD107a|LAMPA|LGP120 HGNC:6499|MIM:153330|Ensembl:ENSG00000185896|HPRD:01076|Vega:OTTHUMG00000017380 13 13q34 lysosomal-associated membrane protein 1 protein-coding lysosomal-associated membrane protein 1 Post-miR-9-3p transfection array studies showed a significant global decline in autophagy gene expression (most notably in PIK3C3, mTOR, and LAMP-1). Autophagy gene mRNAs were generally overexpressed in sporadic (vs. hereditary MTC) and Beclin-1 overexpression was shown to correlate with residual disease. Autophagy is a tumor cell survival mechanism in MTC that when disabled, is of therapeutic advantage. Beclin-1 expression may be a useful prognostic biomarker of aggressive disease. 391 miR-9-3p hsa-miR-9-3p MIMAT0000442 miRNA MTOR autophagy down Homo sapiens medullary thyroid carcinoma cell 25487826 9606 2475 FRAP|FRAP1|FRAP2|RAFT1|RAPT1 HGNC:3942|MIM:601231|Ensembl:ENSG00000198793|HPRD:03134|Vega:OTTHUMG00000002001 1 1p36.2 mechanistic target of rapamycin (serine/threonine kinase) protein-coding mechanistic target of rapamycin (serine/threonine kinase) Post-miR-9-3p transfection array studies showed a significant global decline in autophagy gene expression (most notably in PIK3C3, mTOR, and LAMP-1). Autophagy gene mRNAs were generally overexpressed in sporadic (vs. hereditary MTC) and Beclin-1 overexpression was shown to correlate with residual disease. Autophagy is a tumor cell survival mechanism in MTC that when disabled, is of therapeutic advantage. Beclin-1 expression may be a useful prognostic biomarker of aggressive disease. 392 miR-9-3p hsa-miR-9-3p MIMAT0000442 miRNA PIK3C3 autophagy down Homo sapiens medullary thyroid carcinoma cell 25487826 9606 5289 VPS34|hVps34 HGNC:8974|MIM:602609|HPRD:04009 18 18q12.3 phosphatidylinositol 3-kinase, catalytic subunit type 3 protein-coding phosphatidylinositol 3-kinase, catalytic subunit type 3 Post-miR-9-3p transfection array studies showed a significant global decline in autophagy gene expression (most notably in PIK3C3, mTOR, and LAMP-1). Autophagy gene mRNAs were generally overexpressed in sporadic (vs. hereditary MTC) and Beclin-1 overexpression was shown to correlate with residual disease. Autophagy is a tumor cell survival mechanism in MTC that when disabled, is of therapeutic advantage. Beclin-1 expression may be a useful prognostic biomarker of aggressive disease. 393 miR-95 hsa-miR-95-5p,hsa-miR-95-3p MIMAT0026473,MIMAT0000094 miRNA SUMF1 autophagy down Homo sapiens 25524633 9606 285362 AAPA3037|FGE HGNC:20376|MIM:607939|Ensembl:ENSG00000144455|HPRD:06399|Vega:OTTHUMG00000090269 3 3p26.1 sulfatase modifying factor 1 protein-coding sulfatase modifying factor 1 miR-95 depletes SUMF1 protein levels and suppresses sulfatase activity, causing the disruption of proteoglycan catabolism and lysosomal function. This blocks autophagy-mediated degradation,causing cytoplasmic accumulation of autophagosomes and autophagic substrates. 394 miR-98 hsa-miR-96-5p,hsa-miR-96-3p MIMAT0000095,MIMAT0004510 miRNA PIK3C3 autophagy down Homo sapiens 22135297 9606 5289 VPS34|hVps34 HGNC:8974|MIM:602609|HPRD:04009 18 18q12.3 phosphatidylinositol 3-kinase, catalytic subunit type 3 protein-coding phosphatidylinositol 3-kinase, catalytic subunit type 3 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 395 miR-98 hsa-miR-96-5p,hsa-miR-96-3p MIMAT0000095,MIMAT0004510 miRNA RB1CC1 autophagy down Homo sapiens 22135297 9606 9821 ATG17|CC1|FIP200|PPP1R131 HGNC:15574|MIM:606837|Ensembl:ENSG00000023287|HPRD:06019|Vega:OTTHUMG00000164268 8 8q11 RB1-inducible coiled-coil 1 protein-coding RB1-inducible coiled-coil 1 This autophagy associated entry comes from "T¨¹rei D1, F?ldv¨¢ri-Nagy L, Fazekas D, M¨®dos D. Autophagy Regulatory Network ¡ª A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy. Autophagy 2015; PMID:25635527;". 396 7SK http://lncrna.com/7SK/ lncRNA apoptosis down Homo sapiens embryonic kidney 25492483 9606 protein coding 7SK small nuclear RNA (snRNA) is a 331-333-bp non-coding RNA, which recruits HEXIM 1/2 protein to inhibit positive elongation factor b (P-TEFb) activity. Moreover, 7SK snRNA over-expression promoted apoptosis in cancerous cells. 397 ab074278 lncRNA EMP1 apoptosis Homo sapiens bladder cell 25165097 9606 2012 CL-20|EMP-1|TMP HGNC:3333|MIM:602333|Ensembl:ENSG00000134531|HPRD:11892|Vega:OTTHUMG00000168775 12 12p12.3 epithelial membrane protein 1 protein-coding epithelial membrane protein 1 We identified 32 lncRNAs with potential roles in disease progression. Focusing upon a promising candidate, we implicate upregulation of AB074278 in apoptosis avoidance and the maintenance of a proproliferative state in cancer through a potential interaction with EMP1, a tumor suppressor and a negative regulator of cell proliferation. 398 AF118081 lncRNA apoptosis Homo sapiens 16HBE cell 25050996 9606 Using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), lncRNA AF118081 was identified as the most significantly overexpressed lncRNA in 16HBE-T cells, lung cancer cells, and patient samples. Cell proliferation, colony formation, apoptosis, migration, and invasion were assayed in 16HBE-T cells following the knockdown of lncRNA AF118081 with small interfering RNA. 399 AFAP1-AS1 http://www.lncrnadb.org/afap1as/ lncRNA apoptosis down Homo sapiens Barrett's esophagus 23333711 9606 Its silencing by small interfering RNA inhibited proliferation and colony-forming ability, induced apoptosis, and reduced EAC cell migration and invasion without altering the expression of its protein-coding counterpart, AFAP1. 400 ANRIL http://lncrna.com/ANRIL/ lncRNA CDKN2B apoptosis down Homo sapiens prostate cancer cells 20729297 9606 1030 CDK4I|INK4B|MTS2|P15|TP15|p15INK4b HGNC:1788|MIM:600431|Ensembl:ENSG00000147883|HPRD:02696|Vega:OTTHUMG00000019691 9 9p21 cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) protein-coding cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) CDK inhibitory protein; C The antisense ncRNA ANRIL controls expression in the INK4A/ARF locus comprising the tumor-suppressor genes INK4n/ARF/INK4a, p16/CDKN2A and p15/CDKN2B, which regulate cell cycle progression and senescence. 401 ANRIL http://lncrna.com/ANRIL/ lncRNA CDKN2B apoptosis down Homo sapiens lung 25504755 9606 1030 CDK4I|INK4B|MTS2|P15|TP15|p15INK4b HGNC:1788|MIM:600431|Ensembl:ENSG00000147883|HPRD:02696|Vega:OTTHUMG00000019691 9 9p21 cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) protein-coding cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) LncRNA ANRIL was first found to be required for the PRC2 recruitment to and silencing of p15(INK4B), the expression of which is induced by the ATM-E2F1 signaling pathway. 402 ANRIL http://lncrna.com/ANRIL/ lncRNA E2F1 apoptosis Homo sapiens 23416462 9606 1869 E2F-1|RBAP1|RBBP3|RBP3 HGNC:3113|MIM:189971|Ensembl:ENSG00000101412|HPRD:01806|Vega:OTTHUMG00000032265 20 20q11.2 E2F transcription factor 1 protein-coding E2F transcription factor 1 Consistent with the results from the apoptosis assays, depletion of ANRIL resulted in an increase in the sensitivity of HCT116 p53+/+ cells to the treatment with neocarzinostatin (NCS), confirming that lowered levels of ANRIL in cells led to elevated apoptosis in the DNA damage response(DDR).In the present study, we demonstrate that one specific lncRNA, ANRIL, is transcriptionally up-regulated by the transcription factor E2F1 in an ATM-dependent manner following DNA damage, 403 ANRIL http://lncrna.com/ANRIL/ lncRNA KLF2 apoptosis down Homo sapiens lung 25504755 9606 10365 LKLF HGNC:6347|MIM:602016|Ensembl:ENSG00000127528|HPRD:03602|Vega:OTTHUMG00000182330 19 19p13.11 Kruppel-like factor 2 protein-coding Kruppel-like factor 2 In addition, taking advantage of loss-of-function experiments in NSCLC cells,we found that knockdown of ANRIL expression could impair cell proliferation and induce cell apoptosis both in vitro and vivo through silencing of KLF2 and P21 transcription. 404 ANRIL http://lncrna.com/ANRIL/ lncRNA RASA1 apoptosis down Homo sapiens 25501747 9606 5921 CM-AVM|CMAVM|GAP|PKWS|RASA|RASGAP|p120GAP|p120RASGAP HGNC:9871|MIM:139150|Ensembl:ENSG00000145715|HPRD:00745|Vega:OTTHUMG00000162605 5 5q13.3 RAS p21 protein activator (GTPase activating protein) 1 protein-coding RAS p21 protein activator (GTPase activating protein) 1 Here, we show that the exogenous and endogenous expression of an oncogenic form of small GTPase Ras (called oncogenic Ras) decrease the expression of lncRNA ANRIL (antisense non-coding RNA in the INK4 locus), which is involved in the regulation of cellular senescence 405 ANRIL http://lncrna.com/ANRIL/ lncRNA apoptosis Homo sapiens vascular smooth muscle cells 22382030 9606 ANRIL splicing variants play a role in coordinating tissue remodeling, by modulating the expression of genes involved in cell proliferation, apoptosis, extra-cellular matrix remodeling and inflammatory response to finally impact in the risk of cardiovascular disease and other pathologies. 406 ANRIL http://lncrna.com/ANRIL/ lncRNA apoptosis up Homo sapiens breast cancer cells 22487937 9606 Our results reveal that basal RNA expression levels as well as the changes in the lncRNA expression rates during genotoxic stress-induced apoptosis were cell-type and/or DNA-damaging agent-specific. Generally, we found that some of the RNA molecules (HOTAIR and MALAT1) are down-regulated while many of them (lincRNA-p21, GAS5, MEG3, ANRIL, and ncRNA-CCND1) are up-regulated and some others (TUG1, UCA1, and PANDA) not affected. 407 ANRIL http://lncrna.com/ANRIL/ lncRNA apoptosis Homo sapiens 23861667 9606 Here, we report on the molecular mechanisms through which ANRIL regulates target-genes in trans, leading to increased cell proliferation, increased cell adhesion and decreased apoptosis 408 ASLNC04080 lncRNA apoptosis Homo sapiens HEC-1-B cell 25695231 9606 Expression inhibition of lncRNA ASLNC04080 in HEC-1-B cells caused repression of cell proliferation, increased cell apoptosis, and G1 phase arrest. These results suggested a potential function of ASLNC04080 in endometrial carcinoma genesis and progression. 409 ASncmtRNAs http://www.lncrnadb.org/asncmtrnas/ lncRNA BIRC5 apoptosis down Homo sapiens 25100722 9606 332 API4|EPR-1 HGNC:593|MIM:603352|Ensembl:ENSG00000089685|HPRD:04520|Vega:OTTHUMG00000177505 17 17q25 baculoviral IAP repeat containing 5 protein-coding baculoviral IAP repeat containing 5 Down-regulation of survivin is at the translational level and is probably mediated by microRNAs generated by dicing of the double-stranded stem of the ASncmtRNAs, as suggested by evidence presented here, in which the ASncmtRNAs are bound to Dicer and knockdown of the ASncmtRNAs reduces reporter luciferase activity in a vector carrying the 3'-UTR of survivin mRNA. 410 ASncmtRNAs http://www.lncrnadb.org/asncmtrnas/ lncRNA DICER1 apoptosis Homo sapiens 25100722 9606 23405 DCR1|Dicer|HERNA|MNG1|RMSE2 HGNC:17098|MIM:606241|Ensembl:ENSG00000100697|HPRD:05875|Vega:OTTHUMG00000166134 14 14q32.13 dicer 1, ribonuclease type III protein-coding dicer 1, ribonuclease type III Down-regulation of survivin is at the translational level and is probably mediated by microRNAs generated by dicing of the double-stranded stem of the ASncmtRNAs, as suggested by evidence presented here, in which the ASncmtRNAs are bound to Dicer and knockdown of the ASncmtRNAs reduces reporter luciferase activity in a vector carrying the 3'-UTR of survivin mRNA. 411 BALR-2 lncRNA apoptosis Homo sapiens lymphoblastic cell 25681502 9606 Importantly, high expression of BALR-2 correlated with poor overall survival and diminished response to prednisone treatment. In line with a function for this lncRNA in regulating cell survival, BALR-2 knockdown led to reduced proliferation, increased apoptosis, and increased sensitivity to prednisolone treatment. Conversely, overexpression of BALR-2 led to increased cell growth and resistance to prednisone treatment. Interestingly, BALR-2 expression was repressed by prednisolone treatment and its knockdown led to upregulation of the glucocorticoid response pathway in both human and mouse B-cells. Together, these findings indicate that BALR-2 plays a functional role in the pathogenesis and/or clinical responsiveness of B-ALL and that altering the levels of particular lncRNAs may provide a future direction for therapeutic development. Implications: lncRNA expression has the potential to segregate the common subtypes of B-ALL, predict the cytogenetic subtype, and indicate prognosis. 412 BANCR http://lncrna.com/bancr/ lncRNA CDH1 apoptosis Homo sapiens lung 24655544 9606 999 Arc-1|CD324|CDHE|ECAD|LCAM|UVO HGNC:1748|MIM:192090|Ensembl:ENSG00000039068|HPRD:01885|Vega:OTTHUMG00000137561 16 16q22.1 cadherin 1, type 1, E-cadherin (epithelial) protein-coding cadherin 1, type 1, E-cadherin (epithelial) upregulation of BANCR expression promoted apoptosis.BANCR was found to play a key role in epithelial-mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin and Vimentin expression of BANCR expression promoted apoptosis in comparison with that in control cells 413 BANCR http://lncrna.com/bancr/ lncRNA CDH2 apoptosis Homo sapiens lung 24655544 9606 1000 CD325|CDHN|CDw325|NCAD HGNC:1759|MIM:114020|Ensembl:ENSG00000170558|HPRD:00226|Vega:OTTHUMG00000059940 18 18q11.2 cadherin 2, type 1, N-cadherin (neuronal) protein-coding cadherin 2, type 1, N-cadherin (neuronal) upregulation of BANCR expression promoted apoptosis.BANCR was found to play a key role in epithelial-mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin and Vimentin expression of BANCR expression promoted apoptosis in comparison with that in control cells 414 BANCR http://lncrna.com/bancr/ lncRNA MAP2K7 apoptosis Homo sapiens lung 25661343 9606 5609 JNKK2|MAPKK7|MEK|MEK 7|MKK7|PRKMK7|SAPKK-4|SAPKK4 HGNC:6847|MIM:603014|Ensembl:ENSG00000076984|Vega:OTTHUMG00000137368 19 19p13.3-p13.2 mitogen-activated protein kinase kinase 7 protein-coding mitogen-activated protein kinase kinase 7 We further found that MAPK pathways were involved in the BANCR-mediated cell proliferation and migration of LC. Moreover, BANCR was found to regulate LC proliferation and migration via not ERK MAPK, but p41 MAPK and JNK inactivations. 415 BANCR http://lncrna.com/bancr/ lncRNA MAPK11 apoptosis Homo sapiens lung 25661343 9606 5600 P38B|P38BETA2|PRKM11|SAPK2|SAPK2B|p38-2|p38Beta HGNC:6873|MIM:602898|Ensembl:ENSG00000185386|HPRD:04208|Vega:OTTHUMG00000150226 22 22q13.33 mitogen-activated protein kinase 11 protein-coding mitogen-activated protein kinase 11 We further found that MAPK pathways were involved in the BANCR-mediated cell proliferation and migration of LC. Moreover, BANCR was found to regulate LC proliferation and migration via not ERK MAPK, but p39 MAPK and JNK inactivations. 416 BANCR http://lncrna.com/bancr/ lncRNA MAPK8 apoptosis Homo sapiens lung 25661343 9606 5599 JNK|JNK-46|JNK1|JNK1A2|JNK21B1/2|PRKM8|SAPK1|SAPK1c HGNC:6881|MIM:601158|Ensembl:ENSG00000107643|HPRD:03100|Vega:OTTHUMG00000018172 10 10q11.22 mitogen-activated protein kinase 8 protein-coding mitogen-activated protein kinase 8 We further found that MAPK pathways were involved in the BANCR-mediated cell proliferation and migration of LC. Moreover, BANCR was found to regulate LC proliferation and migration via not ERK MAPK, but p38 MAPK and JNK inactivations. 417 BANCR http://lncrna.com/bancr/ lncRNA MAPK9 apoptosis Homo sapiens lung 25661343 9606 5601 JNK-55|JNK2|JNK2A|JNK2ALPHA|JNK2B|JNK2BETA|PRKM9|SAPK|SAPK1a|p54a|p54aSAPK HGNC:6886|MIM:602896|Ensembl:ENSG00000050748|HPRD:04206|Vega:OTTHUMG00000130934 5 5q35 mitogen-activated protein kinase 9 protein-coding mitogen-activated protein kinase 9 We further found that MAPK pathways were involved in the BANCR-mediated cell proliferation and migration of LC. Moreover, BANCR was found to regulate LC proliferation and migration via not ERK MAPK, but p40 MAPK and JNK inactivations. 418 BANCR http://lncrna.com/bancr/ lncRNA VIM apoptosis Homo sapiens lung 24655544 9606 7431 CTRCT30|HEL113 HGNC:12692|MIM:193060|Ensembl:ENSG00000026025|HPRD:01899|Vega:OTTHUMG00000017744 10 10p13 vimentin protein-coding vimentin upregulation of BANCR expression promoted apoptosis.BANCR was found to play a key role in epithelial-mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin and Vimentin expression of BANCR expression promoted apoptosis in comparison with that in control cells 419 beta2.7 http://lncrna.com/beta27rna/ lncRNA apoptosis Homo sapiens 17540903 9606 we found that human cytomegalovirus infection protected cells from rotenone-induced apoptosis, a protection mediated by a 2.7-kilobase virally encoded RNA (beta2.7). During infection, beta2.7 RNA interacted with complex I and prevented the relocalization of the essential subunit genes associated with retinoid/interferon-induced mortality-19, in response to apoptotic stimuli. 420 CADM1-AS1 lncRNA CADM1 apoptosis Homo sapiens renal cell 25031695 9606 23705 BL2|IGSF4|IGSF4A|NECL2|Necl-2|RA175|ST17|SYNCAM|TSLC1|sTSLC-1|sgIGSF|synCAM1 HGNC:5951|MIM:605686|Ensembl:ENSG00000182985|HPRD:05746|Vega:OTTHUMG00000168202 11 11q23.2 cell adhesion molecule 1 protein-coding cell adhesion molecule 1 Functional experiments demonstrated markedly enhanced ability of growth and migration, and reduced apoptotic rate in CADM1-AS1 knocking down in 786-O cells. Conversely, overexpression of CADM1-AS1 showed a significant decrease in growth and migration, along with an increase in apoptotic rate in ACHN cells. In conclusion, our data demonstrated CADM1-AS1 is a new tumor suppressor in ccRCC which regulates cell proliferation, apoptosis and migration via the expression pattern of "CADM1-AS1/CADM1 mRNA gene pairs". CADM1-AS1 may be a potential biomarker and therapeutic target in patients with ccRCC. 421 CARLo-5 http://lncrna.com/ccat1/ lncRNA MAPK1 apoptosis up Homo sapiens gastric cancer cell 25674211 9606 5594 ERK|ERK-2|ERK2|ERT1|MAPK2|P42MAPK|PRKM1|PRKM2|p38|p40|p41|p41mapk|p42-MAPK HGNC:6871|MIM:176948|Ensembl:ENSG00000100030|HPRD:01496|Vega:OTTHUMG00000030508 22 22q11.21 mitogen-activated protein kinase 1 protein-coding mitogen-activated protein kinase 1 Knockdown of CARLo-5 in gastric cancer cell lines significantly inhibited the cell proliferation via inducing G0/G1 cell-cycle arrest and apoptosis. Furthermore, ERK/MAPK pathway was found to be inactivated in the gastric cells after CARLo-5 knockdown. These results indicated that CARLo-5 might serve as a pro-oncogenic lncRNA that promotes proliferation of gastric cancer and activates the ERK/MAPK pathway. 422 cbr3-as1 http://www.ncbi.nlm.nih.gov/gene/term=naPINK1 lncRNA PINK1 apoptosis Homo sapiens neuronal cells 17362513 9606 65018 BRPK|PARK6 HGNC:14581|MIM:608309|Ensembl:ENSG00000158828|HPRD:10514|Vega:OTTHUMG00000002841 1 1p36 PTEN induced putative kinase 1 protein-coding PTEN induced putative kinase 1 PTEN-induced putative kin PINK1 inhibits mitochondrial cytochrome c release, attenuating the general apoptosis machinery. The observation of concordant regulation of svPINK1 and naPINK1 during in vivo mitochondrial biogenesis was confirmed using RNAi, where selective targeting of naPINK1 results in loss of the PINK1 splice variant in neuronal cell lines. 423 CHRF http://lncrna.com/chrf/ lncRNA MYD88 apoptosis Homo sapiens cardiac 24557880 9606 4615 MYD88D HGNC:7562|MIM:602170|Ensembl:ENSG00000172936|HPRD:03703|Vega:OTTHUMG00000131083 3 3p22 myeloid differentiation primary response 88 protein-coding myeloid differentiation primary response 88 In the animal model, enforced expression of CHRF increased the apoptosis of cardiomyocytes.CHRF is able to directly bind to miR-489 and regulate Myd88 expression and hypertrophy. 424 DQ786227 http://lncrna.com/dq786227/ lncRNA apoptosis Homo sapiens lung 24084393 9606 Silencing of lncRNA-DQ786227 expression in malignant transformed BEAS-2B cells led to inhibition of cell proliferation and colony formation, and increased apoptosis. 425 EBER1(EBV) http://www.lncrnadb.org/EBER1andEBER2RNAs/ lncRNA BCL2 apoptosis down Homo sapiens BL cells 19886912 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 In BL cells, EBERs bind the double-stranded RNA-activated protein kinase PKR,inhibit its phosphorylation, and thereby prevent IFN-alpha-mediated apoptosis. 426 EBER1(EBV) http://www.lncrnadb.org/EBER1andEBER2RNAs/ lncRNA PRKRA apoptosis down Homo sapiens 16160154 9606 8575 DYT16|PACT|RAX HGNC:9438|MIM:603424|Ensembl:ENSG00000180228|HPRD:04573|Vega:OTTHUMG00000132576 2 2q31.2 protein kinase, interferon-inducible double stranded RNA dependent activator protein-coding protein kinase, interferon-inducible double stranded RNA dependent activator EBER bound double-stranded RNA-dependent protein kinase R (PKR), an interferon-inducible serine/threonine kinase, and abrogated its kinase activity. 427 EBER1(EBV) http://www.lncrnadb.org/EBER1andEBER2RNAs/ lncRNA PRKRA apoptosis down Homo sapiens BL cells 19886912 9606 8575 DYT16|PACT|RAX HGNC:9438|MIM:603424|Ensembl:ENSG00000180228|HPRD:04573|Vega:OTTHUMG00000132576 2 2q31.2 protein kinase, interferon-inducible double stranded RNA dependent activator protein-coding protein kinase, interferon-inducible double stranded RNA dependent activator In BL cells, EBERs bind the double-stranded RNA-activated protein kinase PKR,inhibit its phosphorylation, and thereby prevent IFN-alpha-mediated apoptosis. 428 fas http://www.valadkhanlab.org/web/cgi-bin/output_1.cgi?name=FAS&genome=h lncRNA apoptosis Homo sapiens leukaemia cells 9375749 9606 These findings suggest that the presence or absence of FAP-1 mRNA expression did not always correlate with relative sensitivity of Fas-mediated growth inhibition. Furthermore, it is assumed that leukaemia/lymphoma cells could possess structural or functional defects of Fas or Fas-associated proteins resulting in the failure to trigger apoptotic cell death. 429 FaS-aS1 lncRNA RBM5 apoptosis down Homo sapiens lymphomas cell 24811343 9606 10181 G15|LUCA15|RMB5 HGNC:9902|MIM:606884|Ensembl:ENSG00000003756|HPRD:06052|Vega:OTTHUMG00000156785 3 3p21.3 RNA binding motif protein 5 protein-coding RNA binding motif protein 5 We found that the alternative splicing of Fas in lymphomas is tightly regulated by a long-noncoding RNA corresponding to an antisense transcript of Fas (FAS-AS1). Levels of FAS-AS1 correlate inversely with production of sFas, and FAS-AS1 binding to the RBM5 inhibits RBM5-mediated exon 6 skipping. 430 fmr1-as1 http://www.genenames.org/data/hgnc_data.php?hgnc_id=39081 lncRNA apoptosis Homo sapiens brain 18213394 9606 FMR4 markedly affected human cell proliferation in vitro; siRNAs knockdown of FMR4 resulted in alterations in the cell cycle and increased apoptosis, while the overexpression of FMR4 caused an increase in cell proliferation. 431 GAS5 http://lncrna.com/GAS5/ lncRNA BIRC3 apoptosis down Homo sapiens prostate cancer cells 10647931 9606 330 AIP1|API2|CIAP2|HAIP1|HIAP1|MALT2|MIHC|RNF49|c-IAP2 HGNC:591|MIM:601721|Ensembl:ENSG00000023445|HPRD:03426|Vega:OTTHUMG00000167324 11 11q22 baculoviral IAP repeat containing 3 protein-coding baculoviral IAP repeat containing 3 In contrast to SRA, GAS5 functions as a "riborepressor": the ncRNA interacts with the DNA binding domain of the glucocorticoid receptors, thus competing with the glucocorticoid response elements in the genome for binding to these receptors. This suppresses the induction of several responsive genes including cellular inhibitor of apoptosis 2 (cIAP2) and ultimately sensitizes cells to apoptosis 432 GAS5 http://lncrna.com/GAS5/ lncRNA BIRC3 apoptosis down Homo sapiens 23383264 9606 330 AIP1|API2|CIAP2|HAIP1|HIAP1|MALT2|MIHC|RNF49|c-IAP2 HGNC:591|MIM:601721|Ensembl:ENSG00000023445|HPRD:03426|Vega:OTTHUMG00000167324 11 11q22 baculoviral IAP repeat containing 3 protein-coding baculoviral IAP repeat containing 3 We found that levels of the GAS5 transcript were elevated owing to prolonged decay rates in response to UPF1 depletion, and consequently the apoptosis-related genes, cIAP2 and SGK1, were down-regulated. In addition, serum starvation also increased the transcript levels of GAS5 because of prolonged decay rates, and conversely decreased levels of cIAP2 and SGK1 mRNA. 433 GAS5 http://lncrna.com/GAS5/ lncRNA CDKN1A apoptosis Homo sapiens gastric 24884417 9606 1026 CAP20|CDKN1|CIP1|MDA-6|P21|SDI1|WAF1|p21CIP1 HGNC:1784|MIM:116899|Ensembl:ENSG00000124762|HPRD:00298|Vega:OTTHUMG00000014603 6 6p21.2 cyclin-dependent kinase inhibitor 1A (p21, Cip1) protein-coding cyclin-dependent kinase inhibitor 1A (p21, Cip1) Ectopic expression of GAS5 was demonstrated to decrease gastric cancer cell proliferation and induce apoptosis in vitro and in vivo, while downregulation of endogenous GAS5 could promote cell proliferation. Finally, we found that GAS5 could influence gastric cancer cells proliferation, partly via regulating E2F1 and P21 expression. 434 GAS5 http://lncrna.com/GAS5/ lncRNA E2F1 apoptosis Homo sapiens gastric 24884417 9606 1869 E2F-1|RBAP1|RBBP3|RBP3 HGNC:3113|MIM:189971|Ensembl:ENSG00000101412|HPRD:01806|Vega:OTTHUMG00000032265 20 20q11.2 E2F transcription factor 1 protein-coding E2F transcription factor 1 Ectopic expression of GAS5 was demonstrated to decrease gastric cancer cell proliferation and induce apoptosis in vitro and in vivo, while downregulation of endogenous GAS5 could promote cell proliferation. Finally, we found that GAS5 could influence gastric cancer cells proliferation, partly via regulating E2F1 and P21 expression. 435 GAS5 http://lncrna.com/GAS5/ lncRNA MTOR apoptosis Homo sapiens breast 24789445 9606 2475 FRAP|FRAP1|FRAP2|RAFT1|RAPT1 HGNC:3942|MIM:601231|Ensembl:ENSG00000198793|HPRD:03134|Vega:OTTHUMG00000002001 1 1p36.2 mechanistic target of rapamycin (serine/threonine kinase) protein-coding mechanistic target of rapamycin (serine/threonine kinase) GAS5 lncRNA promoted the apoptosis of triple-negative and oestrogen receptor-positive cells but only dual PI3K/mTOR inhibition was able to enhance GAS5 levels in all cell types. 436 GAS5 http://lncrna.com/GAS5/ lncRNA PIK3CA apoptosis Homo sapiens breast 24789445 9606 5290 CLOVE|CWS5|MCAP|MCM|MCMTC|PI3K|p110-alpha HGNC:8975|MIM:171834|HPRD:01382 3 3q26.3 phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha protein-coding phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha GAS5 lncRNA promoted the apoptosis of triple-negative and oestrogen receptor-positive cells but only dual PI3K/mTOR inhibition was able to enhance GAS5 levels in all cell types. 437 Gas5 http://lncrna.com/GAS5/ lncRNA SCTR apoptosis Homo sapiens 25377354 9606 6344 SR HGNC:10608|MIM:182098|Ensembl:ENSG00000080293|HPRD:01628|Vega:OTTHUMG00000131407 2 2q14.1 secretin receptor protein-coding secretin receptor Here we report the molecular requirements for the recognition of steroid receptors (SRs) by the lincRNA growth arrest-specific 5 (Gas5), which regulates steroid-mediated transcriptional regulation, growth arrest and apoptosis. 438 GAS5 http://lncrna.com/GAS5/ lncRNA SGK1 apoptosis down Homo sapiens 23383264 9606 6446 SGK HGNC:10810|MIM:602958|Ensembl:ENSG00000118515|HPRD:04264|Vega:OTTHUMG00000015613 6 6q23 serum/glucocorticoid regulated kinase 1 protein-coding serum/glucocorticoid regulated kinase 1 We found that levels of the GAS5 transcript were elevated owing to prolonged decay rates in response to UPF1 depletion, and consequently the apoptosis-related genes, cIAP2 and SGK1, were down-regulated. In addition, serum starvation also increased the transcript levels of GAS5 because of prolonged decay rates, and conversely decreased levels of cIAP2 and SGK1 mRNA. 439 GAS5 http://lncrna.com/GAS5/ lncRNA apoptosis Homo sapiens T-cell lines 18354083 9606 Overexpression of GAS5 causes both an increase in apoptosis and a reduction in the rate of progression through the cell-cycle. 440 GAS5 http://lncrna.com/GAS5/ lncRNA apoptosis Homo sapiens breast cancer cells 18836484 9606 GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. 441 GAS5 http://lncrna.com/GAS5/ lncRNA apoptosis up Homo sapiens breast cancer cells 22487937 9606 Our results reveal that basal RNA expression levels as well as the changes in the lncRNA expression rates during genotoxic stress-induced apoptosis were cell-type and/or DNA-damaging agent-specific. Generally, we found that some of the RNA molecules (HOTAIR and MALAT1) are down-regulated while many of them (lincRNA-p21, GAS5, MEG3, ANRIL, and ncRNA-CCND1) are up-regulated and some others (TUG1, UCA1, and PANDA) not affected. 442 GAS5 http://lncrna.com/GAS5/ lncRNA apoptosis Homo sapiens Renal cell carcinoma 23621190 9606 Furthermore, using functional expression cloning, we found that overexpression of GAS5 in A498 cells inhibited cell proliferation, induced cell apoptosis and arrested cell cycling. 443 GAS5 http://lncrna.com/GAS5/ lncRNA apoptosis Homo sapiens prostate 23676682 9606 Prostate cell lines were transfected with GAS5-encoding plasmids or GAS5 siRNAs, and cell survival was assessed. Basal apoptosis increased, and cell survival decreased 444 GAS5 http://lncrna.com/GAS5/ lncRNA apoptosis Homo sapiens NSCLC 24357161 9606 7157 TP53|BCC7|LFS1|TRP53 HGNC:11998|Ensembl:ENSG00000141510|HPRD:01859|MIM:191170|Vega:OTTHUMG00000162125 17 17p13.1 tumor protein p53 protein coding tumor protein p53 Furthermore, GAS5 overexpression increased tumor cell growth arrest and induced apoptosis in vitro and in vivo.we found that ectopic expression of GAS5 significantly up-regulated p53 expression and down-regulated transcription factor E2F1 expression. 445 H19 http://lncrna.com/H19/ lncRNA ABL1 apoptosis down Homo sapiens leukemia 24685695 9606 25 ABL|JTK7|bcr/abl|c-ABL|c-ABL1|p150|v-abl HGNC:76|MIM:189980|Ensembl:ENSG00000097007|HPRD:01809|Vega:OTTHUMG00000020813 9 9q34.1 ABL proto-oncogene 1, non-receptor tyrosine kinase protein-coding ABL proto-oncogene 1, non-receptor tyrosine kinase Silencing H19 expression sensitized leukemic cells to undergo imatinib-induced apoptosis and inhibited Bcr-Abl-induced tumor growth. Furthermore, H19 was shown to be regulated by c-Myc in Bcr-Abl-expressing cells. 446 H19 http://lncrna.com/H19/ lncRNA BCR apoptosis down Homo sapiens leukemia 24685695 9606 613 ALL|BCR1|CML|D22S11|D22S662|PHL HGNC:1014|MIM:151410|Ensembl:ENSG00000186716|HPRD:01044|Vega:OTTHUMG00000150655 22 22q11.23 breakpoint cluster region protein-coding breakpoint cluster region Silencing H19 expression sensitized leukemic cells to undergo imatinib-induced apoptosis and inhibited Bcr-Abl-induced tumor growth. Furthermore, H19 was shown to be regulated by c-Myc in Bcr-Abl-expressing cells. 447 H19 http://lncrna.com/H19/ lncRNA DUSP5 apoptosis down Homo sapiens JAR cells 23711233 9606 1847 DUSP|HVH3 HGNC:3071|MIM:603069|Ensembl:ENSG00000138166|HPRD:04349|Vega:OTTHUMG00000019040 10 10q25 dual specificity phosphatase 5 protein-coding dual specificity phosphatase 5 H19 knockdown inhibited apoptosis and proliferation of JAR cells, but had no significant impact on cell invasion. In addition, H19 knockdown resulted in significant upregulation of HES-1 and DUSP5 expression, but not IGF2 expression in JAR cells. 448 H19 http://lncrna.com/H19/ lncRNA HES1 apoptosis down Homo sapiens JAR cells 23711233 9606 3280 HES-1|HHL|HRY|bHLHb39 HGNC:5192|MIM:139605|Ensembl:ENSG00000114315|HPRD:00770|Vega:OTTHUMG00000155984 3 3q28-q29 hes family bHLH transcription factor 1 protein-coding hes family bHLH transcription factor 1 H19 knockdown inhibited apoptosis and proliferation of JAR cells, but had no significant impact on cell invasion. In addition, H19 knockdown resulted in significant upregulation of HES-1 and DUSP5 expression, but not IGF2 expression in JAR cells. 449 H19 http://lncrna.com/H19/ lncRNA MYC apoptosis down Homo sapiens leukemia 24685695 9606 4609 MRTL|MYCC|bHLHe39|c-Myc HGNC:7553|MIM:190080|Ensembl:ENSG00000136997|HPRD:01818|Vega:OTTHUMG00000128475 8 8q24.21 v-myc avian myelocytomatosis viral oncogene homolog protein-coding v-myc avian myelocytomatosis viral oncogene homolog Silencing H19 expression sensitized leukemic cells to undergo imatinib-induced apoptosis and inhibited Bcr-Abl-induced tumor growth. Furthermore, H19 was shown to be regulated by c-Myc in Bcr-Abl-expressing cells. 450 h19 http://lncrna.com/H19/ lncRNA TP53 apoptosis down Homo sapiens gastric cancer cells 22776265 9606 7157 BCC7|LFS1|P53|TRP53 HGNC:11998|MIM:191170|Ensembl:ENSG00000141510|HPRD:01859|Vega:OTTHUMG00000162125 17 17p13.1 tumor protein p53 protein-coding tumor protein p53 antigen NY-CO-13; cellula Ectopic expression of H19 increased cell proliferation, whereas H19 siRNA treatment contributed to cell apoptosis in AGS cell line.We further verified that H19 was associated with p53, and that this association resulted in partial p53 inactivation 451 HIF1A-AS1 lncRNA BCL2 apoptosis up Homo sapiens vascular 25550800 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 Regulation of apoptosis by long non-coding RNA HIF1A-AS1 in VSMCs: implications for TAA pathogenesis. We also found that transfection of cells with HIF1a-AS1 siRNA decreased the expression of caspase3 and caspase8 and increased the expression of Bcl2, and protected PA-induced cell apoptosis in VSMCs. 452 HIF1A-AS1 lncRNA CASP3 apoptosis down Homo sapiens vascular 25550800 9606 836 CPP32|CPP32B|SCA-1 HGNC:1504|MIM:600636|Ensembl:ENSG00000164305|HPRD:02799|Vega:OTTHUMG00000133681 4 4q34 caspase 3, apoptosis-related cysteine peptidase protein-coding caspase 3, apoptosis-related cysteine peptidase Regulation of apoptosis by long non-coding RNA HIF1A-AS1 in VSMCs: implications for TAA pathogenesis. We also found that transfection of cells with HIF1a-AS1 siRNA decreased the expression of caspase3 and caspase8 and increased the expression of Bcl2, and protected PA-induced cell apoptosis in VSMCs. 453 HIF1A-AS1 lncRNA CASP8 apoptosis down Homo sapiens vascular 25550800 9606 841 ALPS2B|CAP4|Casp-8|FLICE|MACH|MCH5 HGNC:1509|MIM:601763|Ensembl:ENSG00000064012|HPRD:03459|Vega:OTTHUMG00000132821 2 2q33-q34 caspase 8, apoptosis-related cysteine peptidase protein-coding caspase 8, apoptosis-related cysteine peptidase Regulation of apoptosis by long non-coding RNA HIF1A-AS1 in VSMCs: implications for TAA pathogenesis. We also found that transfection of cells with HIF1a-AS1 siRNA decreased the expression of caspase3 and caspase8 and increased the expression of Bcl2, and protected PA-induced cell apoptosis in VSMCs. 454 HIF1A-AS1 lncRNA SMARCA4 apoptosis up Homo sapiens smooth muscle cell 24875884 9606 6597 BAF190|BAF190A|BRG1|MRD16|RTPS2|SNF2|SNF2L4|SNF2LB|SWI2|hSNF2b HGNC:11100|MIM:603254|Ensembl:ENSG00000127616|HPRD:04459|Vega:OTTHUMG00000169272 19 19p13.2 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 protein-coding SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 BRG1 expression is increased in thoracic aortic aneurysms and regulates proliferation and apoptosis of vascular smooth muscle cells through the long non-coding RNA HIF1A-AS1 in vitro. 455 HOTAIR http://lncrna.com/hotair/ lncRNA AKT1 apoptosis down Homo sapiens breast 25613518 9606 207 AKT|CWS6|PKB|PKB-ALPHA|PRKBA|RAC|RAC-ALPHA HGNC:391|MIM:164730|Ensembl:ENSG00000142208|HPRD:01261|Vega:OTTHUMG00000170795 14 14q32.32 v-akt murine thymoma viral oncogene homolog 1 protein-coding v-akt murine thymoma viral oncogene homolog 1 Treatment of MCF-7 cells with calycosin or genistein resulted in decreased phosphorylation of Akt, and decreased expression of its downstream target, HOTAIR. 456 HOTAIR http://lncrna.com/hotair/ lncRNA CDKN1A apoptosis down Homo sapiens lung 24155936 9606 1026 CAP20|CDKN1|CIP1|MDA-6|P21|SDI1|WAF1|p21CIP1 HGNC:1784|MIM:116899|Ensembl:ENSG00000124762|HPRD:00298|Vega:OTTHUMG00000014603 6 6p21.2 cyclin-dependent kinase inhibitor 1A (p21, Cip1) protein-coding cyclin-dependent kinase inhibitor 1A (p21, Cip1) We also found that the siRNA/HOTAIR1-mediated chemosensivity enhancement was associated with inhibition of cell proliferation, induction of G0/G1 cell-cycle arrest and apoptosis enhancement through regulation of p21(WAF1/CIP1) (p21) expression. 457 HOTAIR http://lncrna.com/hotair/ lncRNA CDKN1A apoptosis down Homo sapiens cervical 25547435 9606 1026 CAP20|CDKN1|CIP1|MDA-6|P21|SDI1|WAF1|p21CIP1 HGNC:1784|MIM:116899|Ensembl:ENSG00000124762|HPRD:00298|Vega:OTTHUMG00000014603 6 6p21.2 cyclin-dependent kinase inhibitor 1A (p21, Cip1) protein-coding cyclin-dependent kinase inhibitor 1A (p21, Cip1) In vitro,upregulation of HOTAIR inhibited apoptosis and promoted cellular proliferation,cell cycle progression, migration, and invasion; Moreover, we proved that HOTAIR execute its functions mainly through inhibiting the p21 expression. 458 HOTAIR http://lncrna.com/hotair/ lncRNA CREBBP apoptosis down Homo sapiens breast 23375982 9606 1387 CBP|KAT3A|RSTS HGNC:2348|MIM:600140|Ensembl:ENSG00000005339|HPRD:02534|Vega:OTTHUMG00000129431 16 16p13.3 CREB binding protein protein-coding CREB binding protein Herein, we demonstrated that HOTAIR is crucial for cell growth and viability and its knockdown induced apoptosis in breast cancer cells. We also demonstrated that HOTAIR is transcriptionally induced by estradiol (E2). Its promoter contains multiple functional estrogen response elements (EREs). Estrogen receptors (ERs) along with various ER coregulators such as histone methylases MLL1 (mixed lineage leukemia 1) and MLL3 and CREB-binding protein/p300 bind to the promoter of HOTAIR in an E2-dependent manner. 459 HOTAIR http://lncrna.com/hotair/ lncRNA EP300 apoptosis down Homo sapiens breast 23375982 9606 2033 KAT3B|RSTS2|p300 HGNC:3373|MIM:602700|Ensembl:ENSG00000100393|HPRD:04078|Vega:OTTHUMG00000150937 22 22q13.2 E1A binding protein p300 protein-coding E1A binding protein p300 Herein, we demonstrated that HOTAIR is crucial for cell growth and viability and its knockdown induced apoptosis in breast cancer cells. We also demonstrated that HOTAIR is transcriptionally induced by estradiol (E2). Its promoter contains multiple functional estrogen response elements (EREs). Estrogen receptors (ERs) along with various ER coregulators such as histone methylases MLL1 (mixed lineage leukemia 1) and MLL3 and CREB-binding protein/p300 bind to the promoter of HOTAIR in an E2-dependent manner. 460 HOTAIR http://lncrna.com/hotair/ lncRNA ESR1 apoptosis down Homo sapiens breast 23375982 9606 2099 ER|ESR|ESRA|ESTRR|Era|NR3A1 HGNC:3467|MIM:133430|Ensembl:ENSG00000091831|HPRD:00589|Vega:OTTHUMG00000016103 6 6q25.1 estrogen receptor 1 protein-coding estrogen receptor 1 Herein, we demonstrated that HOTAIR is crucial for cell growth and viability and its knockdown induced apoptosis in breast cancer cells. We also demonstrated that HOTAIR is transcriptionally induced by estradiol (E2). Its promoter contains multiple functional estrogen response elements (EREs). Estrogen receptors (ERs) along with various ER coregulators such as histone methylases MLL1 (mixed lineage leukemia 1) and MLL3 and CREB-binding protein/p300 bind to the promoter of HOTAIR in an E2-dependent manner. 461 HOTAIR http://lncrna.com/hotair/ lncRNA EZH2 apoptosis Homo sapiens Panc1 and L3.6pL cells 22614017 9606 2146 ENX-1|ENX1|EZH1|EZH2b|KMT6|KMT6A|WVS|WVS2 HGNC:3527|MIM:601573|Ensembl:ENSG00000106462|HPRD:03342|Vega:OTTHUMG00000158973 7 7q35-q36 enhancer of zeste 2 polycomb repressive complex 2 subunit protein-coding enhancer of zeste 2 polycomb repressive complex 2 subunit HOTAIR knockdown in Panc1 and L3.6pL pancreatic cancer cells that overexpress this lincRNA decreased cell proliferation, altered cell cycle progression and induced apoptosis Analysis of selected genes suppressed by HOTAIR in Panc1 and L3.6pL cells showed by knockdown of EZH2 462 HOTAIR http://lncrna.com/hotair/ lncRNA HOXA5 apoptosis down Homo sapiens lung 24103700 9606 3202 HOX1|HOX1.3|HOX1C HGNC:5106|MIM:142952|Ensembl:ENSG00000106004|HPRD:00840|Vega:OTTHUMG00000023214 7 7p15.2 homeobox A5 protein-coding homeobox A5 Taken together, these results indicate that inhibition of HOTAIR induces NSCLC cells apoptosis, but has no effect on cell vitality. Our findings indicate that HOTAIR is significantly up-regulated in NSCLC tissues, and regulates NSCLC cell invasion and metastasis, partially via the down-regulation of HOXA5. 463 HOTAIR http://lncrna.com/hotair/ lncRNA KMT2A apoptosis down Homo sapiens breast 23375982 9606 4297 ALL-1|CXXC7|HRX|HTRX1|MLL|MLL/GAS7|MLL1|MLL1A|TET1-MLL|TRX1|WDSTS HGNC:7132|MIM:159555|Ensembl:ENSG00000118058|HPRD:01162|Vega:OTTHUMG00000166337 11 11q23 lysine (K)-specific methyltransferase 2A protein-coding lysine (K)-specific methyltransferase 2A Herein, we demonstrated that HOTAIR is crucial for cell growth and viability and its knockdown induced apoptosis in breast cancer cells. We also demonstrated that HOTAIR is transcriptionally induced by estradiol (E2). Its promoter contains multiple functional estrogen response elements (EREs). Estrogen receptors (ERs) along with various ER coregulators such as histone methylases MLL1 (mixed lineage leukemia 1) and MLL3 and CREB-binding protein/p300 bind to the promoter of HOTAIR in an E2-dependent manner. 464 HOTAIR http://lncrna.com/hotair/ lncRNA KMT2C apoptosis down Homo sapiens breast 23375982 9606 58508 HALR|MLL3 HGNC:13726|MIM:606833|Ensembl:ENSG00000055609|HPRD:06016|Vega:OTTHUMG00000150553 7 7q36.1 lysine (K)-specific methyltransferase 2C protein-coding lysine (K)-specific methyltransferase 2C Herein, we demonstrated that HOTAIR is crucial for cell growth and viability and its knockdown induced apoptosis in breast cancer cells. We also demonstrated that HOTAIR is transcriptionally induced by estradiol (E2). Its promoter contains multiple functional estrogen response elements (EREs). Estrogen receptors (ERs) along with various ER coregulators such as histone methylases MLL1 (mixed lineage leukemia 1) and MLL3 and CREB-binding protein/p300 bind to the promoter of HOTAIR in an E2-dependent manner. 465 HOTAIR http://lncrna.com/hotair/ lncRNA PTEN apoptosis down Homo sapiens laryngeal squamous cell cancer 23141928 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog SiRNA-mediated knockdown of HOTAIR led to reduced invasion and increased apoptosis of Hep-2 cells in vitro and significantly reduced growth of LSCC xenograft tumors in mice. Moreover, PTEN methylation was significantly reduced in Hep-2 cells depleted of HOTAIR. 466 HOTAIR http://lncrna.com/hotair/ lncRNA RBM38 apoptosis down Homo sapiens hepatocellular carcinoma 24663081 9606 55544 HSRNASEB|RNPC1|SEB4B|SEB4D|dJ800J21.2 HGNC:15818|MIM:612428|Ensembl:ENSG00000132819|HPRD:15268|Vega:OTTHUMG00000032820 20 20q13.31 RNA binding motif protein 38 protein-coding RNA binding motif protein 38 Long non-coding RNA HOTAIR exerts regulatory functions in various biological processes in cancer cells, such as proliferation, apoptosis, mobility, and invasion. HOTAIR could promote migration and invasion of HCC cells by inhibiting RBM38. 467 HOTAIR http://lncrna.com/hotair/ lncRNA TNF apoptosis down Homo sapiens hepatocellular carcinoma cells 21327457 9606 7124 DIF|TNF-alpha|TNFA|TNFSF2 HGNC:11892|MIM:191160|Ensembl:ENSG00000232810|HPRD:01855|Vega:OTTHUMG00000031194 6 6p21.3 tumor necrosis factor protein-coding tumor necrosis factor APC1 protein; TNF, macrop SiRNA suppression of HOTAIR in a liver cancer cell line reduced cell viability and cell invasion, sensitized TNF-a induced apoptosis, and increased the chemotherapeutic sensitivity of cancer cells to cisplatin and doxorubicin. 468 HOTAIR http://lncrna.com/hotair/ lncRNA apoptosis down Homo sapiens breast cancer cells 22487937 9606 Our results reveal that basal RNA expression levels as well as the changes in the lncRNA expression rates during genotoxic stress-induced apoptosis were cell-type and/or DNA-damaging agent-specific. Generally, we found that some of the RNA molecules (HOTAIR and MALAT1) are down-regulated while many of them (lincRNA-p21, GAS5, MEG3, ANRIL, and ncRNA-CCND1) are up-regulated and some others (TUG1, UCA1, and PANDA) not affected. 469 HOTAIR http://lncrna.com/hotair/ lncRNA apoptosis Homo sapiens oesophageal squamous cell carcinoma 24022190 9606 The knockdown of HOTAIR in the KYSE510 and KYSE180 ESCC cell lines using small hairpin RNAs (shRNAs) reduced the ability of the cells to form foci, migrate, and invade the extracellular matrix in culture, altered cell cycle progression, and increased the sensitivity of the cells to apoptosis. 470 HOTAIR http://lncrna.com/hotair/ lncRNA apoptosis Homo sapiens gastric 25063030 9606 We found that HOTAIR was involved in inhibition of apoptosis and promoted invasiveness, supporting a role for HOTAIR in carcinogenesis and progression of gastric cancer. 471 HOXA-AS2 http://www.ncbi.nlm.nih.gov/gene/term=HOXA-AS2++human lncRNA apoptosis down Homo sapiens NB4cells 23649634 9606 8743 TL2|APO2L|CD253|TNFSF10|Apo-2L HGNC:11925|Ensembl:ENSG00000121858|HPRD:04670|MIM:603598|Vega:OTTHUMG00000156917 3 3q26 tumor necrosis factor (ligand) superfamily, member 10 protein coding tumor necrosis factor (ligand) superfamily, member 10 The increase in death of HOXA-AS2 knockdown cells was accompanied by an elevated TNF-related apoptosis-inducing ligand (TRAIL) levels, but ATRA-induced NB4 cells treated with TRAIL did show an increase in HOXA-AS2 expression. 472 htr2a-as1 http://www.genenames.org/data/hgnc_data.php?hgnc_id=40289 lncRNA PCNA apoptosis down Homo sapiens hepatocellular carcinoma cells 17932748 9606 5111 - HGNC:8729|MIM:176740|Ensembl:ENSG00000132646|HPRD:01456|Vega:OTTHUMG00000031798 20 20pter-p12 proliferating cell nuclear antigen protein-coding proliferating cell nuclear antigen DNA polymerase delta auxi HepG2 cells transfected with the antisense hTR gene showed down-regulated telomerase activity, inhibited cell growth, decreased PCNA expression, and increased apoptotic rate. 473 htr2a-as1 http://www.genenames.org/data/hgnc_data.php?hgnc_id=40289 lncRNA apoptosis Homo sapiens malignant glioma cells 17912434 9606 Apoptosis-inducing agents (CDDP and PTX) but not autophagy-inducing therapies (TMZ and IR) enhanced the incidence of apoptosis caused by 2-5A-anti-hTR. 474 HULC http://lncrna.com/HULC/ lncRNA apoptosis Homo sapiens gastric 24247585 9606 Mechanistically, we discovered that overexpression of HULC could induce patterns of autophagy in SGC7901 cells; more importantly, autophagy inhibition increased overexpression of HULC cell apoptosis. 475 INXS lncRNA BCL2L1 apoptosis Homo sapiens kidney tumor cell 24992962 9606 598 BCL-XL/S|BCL2L|BCLX|BCLXL|BCLXS|Bcl-X|PPP1R52|bcl-xL|bcl-xS HGNC:992|MIM:600039|Ensembl:ENSG00000171552|HPRD:02497|Vega:OTTHUMG00000032192 20 20q11.21 BCL2-like 1 protein-coding BCL2-like 1 Three apoptosis-inducing agents increased INXS lncRNA endogenous expression in the 786-O kidney tumor cell line, increased BCL-XS/BCL-XL mRNA ratio and activated caspases 3, 7 and 9. These effects were abrogated in the presence of INXS knockdown. Similarly, ectopic INXS overexpression caused a shift in splicing toward BCL-XS and activation of caspases, thus leading to apoptosis. 476 IPS1 http://lncrna.com/IPS1/ lncRNA apoptosis up ed Homo sapiens breast 25738636 9606 protein coding In the present study, we intended to determine the role of DAP3 in cancer cell behaviour in the context of human breast cancer. We developed knockdown sub-lines of MCF7 and MDA-MB-231.The expression of caspase-9 and IPS1, known components of the apoptosis pathway, were significantly reduced in the MCF7DAP3kd cells (p=0.05 and p=0.003, respectively). 477 Lin28b lncRNA BIRC5 apoptosis up Homo sapiens oral squamous cell 24386298 9606 332 API4|EPR-1 HGNC:593|MIM:603352|Ensembl:ENSG00000089685|HPRD:04520|Vega:OTTHUMG00000177505 17 17q25 baculoviral IAP repeat containing 5 protein-coding baculoviral IAP repeat containing 5 Besides, stable expressing Lin28B in oral cancer cells promoted cell migration, invasion, colony formation, in vivo proliferation and increased the expression of cancer suppressor miRNA let-7 targeted genes IL-6, HMGA2, the EMT markers Snail and Twist, the angiogenesis inducer VEGF, and the apoptosis inhibitor Survivin. These combined results indicate that Lin28B is a novel marker for predicting prognosis in patients with OSCC and may be a therapeutic target. 478 LINC00312 http://lncrna.com/linc00312/ lncRNA apoptosis Homo sapiens nasopharyngeal carcinoma 23529758 9606 The long intergenic non-coding RNA LINC00312, also called NAG7, was first cloned by our group. Our previous studies have found that LINC00312 could inhibit proliferation and induce apoptosis in nasopharynge 479 Linc00974 lncRNA KRT19 apoptosis Homo sapiens hepatocellular carcinoma cell 25476897 9606 3880 CK19|K19|K1CS HGNC:6436|MIM:148020|Ensembl:ENSG00000171345|HPRD:01007|Vega:OTTHUMG00000133422 17 17q21.2 keratin 19 protein-coding keratin 19 Knockdown of Linc00974 resulted in an inhibition of cell proliferation and invasion with an activation of apoptosis and cell cycle arrest in vitro, which was also validated by a subcutaneous and tail vein/intraperitoneal injection xenotransplantation model in vivo. We further investigated the interaction pattern of Linc00974 and KRT19. MiR-642 was identified, by acting as the competing endogenous RNA in regulating Linc00974 and KRT19. Linc00974 was increased owing to an abnormal hypomethylation promoter, which induced the upregulation of KRT19 via ceRNA interaction, resulting in the activation of the Notch and TGF-¦Â pathways as detected by cDNA microarray. 480 LincRNA-EPS http://lncrna.com/lincrna-eps/ lncRNA apoptosis Homo sapiens 22190456 9606 In this issue of Genes & Development, Hu and colleagues (2573-2578) report the discovery of LincRNA erythroid prosurvival (LincRNA-EPS), a murine lncRNA that facilitates red blood cell formation (erythropoiesis) by suppressing apoptosis. 481 lincRNA-p21 http://lncrna.com/lincRNA-p21/ lncRNA CTNNBIP1 apoptosis down Homo sapiens colorectal cancer cell 24573322 9606 56998 ICAT HGNC:16913|MIM:607758|Ensembl:ENSG00000178585|HPRD:09677|Vega:OTTHUMG00000001796 1 1p36.22 catenin, beta interacting protein 1 protein-coding catenin, beta interacting protein 1 By expression profile analysis, we demonstrated that lincRNA-p21 decreases in CRC cell lines and tissue samples, which contributes to the elevation of ¦Â-catenin in CRC. We further showed that lincRNA-p21 increases following X-ray treatment, and enforced expression of the lincRNA enhances the sensitivity of radiotherapy for CRC by promoting cell apoptosis. Suppression of the ¦Â-catenin signaling pathway and elevation of the pro-apoptosis gene Noxa expression may help explain the role of lincRNA-p21 in CRC radiotherapy. 482 lincRNA-p21 http://lncrna.com/lincRNA-p21/ lncRNA PMAIP1 apoptosis up Homo sapiens colorectal cancer cell 24573322 9606 5366 APR|NOXA HGNC:9108|MIM:604959|Ensembl:ENSG00000141682|HPRD:12002|Vega:OTTHUMG00000132765 18 18q21.32 phorbol-12-myristate-13-acetate-induced protein 1 protein-coding phorbol-12-myristate-13-acetate-induced protein 1 By expression profile analysis, we demonstrated that lincRNA-p21 decreases in CRC cell lines and tissue samples, which contributes to the elevation of ¦Â-catenin in CRC. We further showed that lincRNA-p21 increases following X-ray treatment, and enforced expression of the lincRNA enhances the sensitivity of radiotherapy for CRC by promoting cell apoptosis. Suppression of the ¦Â-catenin signaling pathway and elevation of the pro-apoptosis gene Noxa expression may help explain the role of lincRNA-p21 in CRC radiotherapy. 483 lincRNA-p21 http://lncrna.com/lincRNA-p21/ lncRNA apoptosis up Homo sapiens breast cancer cells 22487937 9606 Our results reveal that basal RNA expression levels as well as the changes in the lncRNA expression rates during genotoxic stress-induced apoptosis were cell-type and/or DNA-damaging agent-specific. Generally, we found that some of the RNA molecules (HOTAIR and MALAT1) are down-regulated while many of them (lincRNA-p21, GAS5, MEG3, ANRIL, and ncRNA-CCND1) are up-regulated and some others (TUG1, UCA1, and PANDA) not affected. 484 lincRNA-p21 http://lncrna.com/lincRNA-p21/ lncRNA apoptosis up Homo sapiens smooth muscle cell 25156994 9606 we showed that lincRNA-p21 represses cell proliferation and induces apoptosis in vascular smooth muscle cells and mouse mononuclear macrophage cells in vitro 485 lincRNA-RoR http://lncrna.com/lincRNA-RoR/ lncRNA TGFB1 apoptosis up Homo sapiens Hepatocellular cancers 24918061 9606 7040 CED|DPD1|LAP|TGFB|TGFbeta HGNC:11766|MIM:190180|HPRD:01821 19 19q13.1 transforming growth factor, beta 1 protein-coding transforming growth factor, beta 1 Incubation with HCC-derived extracellular vesicles increased linc-ROR expression and reduced chemotherapy-induced cell death in recipient cells.TGF¦Â selectively enriches linc-RoR within extracellular vesicles, which has a potential role in intercellular signaling in response to TGF¦Â; 486 lincRNA-RoR http://lncrna.com/lincRNA-RoR/ lncRNA TP53 apoptosis down Homo sapiens 23208419 9606 7157 BCC7|LFS1|P53|TRP53 HGNC:11998|MIM:191170|Ensembl:ENSG00000141510|HPRD:01859|Vega:OTTHUMG00000162125 17 17p13.1 tumor protein p53 protein-coding tumor protein p53 antigen NY-CO-13; cellula The human long non-coding RNA-RoR is a p53 repressor in response to DNA damage.RoR inhibits p53-mediated cell cycle arrest and apoptosis. 487 lincRNA-UFC1 lncRNA CTNNB1 apoptosis down Homo sapiens hepatocellular carcinoma cell 25449213 9606 1499 CTNNB|MRD19|armadillo HGNC:2514|MIM:116806|Ensembl:ENSG00000168036|HPRD:00286|Vega:OTTHUMG00000131393 3 3p21 catenin (cadherin-associated protein), beta 1, 88kDa protein-coding catenin (cadherin-associated protein), beta 1, 88kDa Transgenic expression of the lincRNA-UFC1 in HCC cells promoted their proliferation and cell-cycle progression and inhibited apoptosis, whereas short hairpin RNA knockdown of lincRNA-UFC1 had opposite effects. Tumors grown from lincRNA-UFC1 knockdown were smaller than controls. The lincRNA-UFC1 interacted directly with the messenger RNA (mRNA) stabilizing protein HuR (encoded by ELAVL1) to increase levels of ¦Â-catenin mRNA (encoded by CTNNB1) and protein. Levels of lincRNA-UFC1 correlated with those of ¦Â-catenin in HCC tissues.In contrast, there was a negative correlation between levels of microRNA 34a and lincRNA-UFC1 in HCC tissues; microRNA 34a reduced the stability of lincRNA-UFC1. 488 lincRNA-UFC1 lncRNA ELAVL1 apoptosis Homo sapiens hepatocellular carcinoma cell 25449213 9606 1994 ELAV1|HUR|Hua|MelG HGNC:3312|MIM:603466|Ensembl:ENSG00000066044|HPRD:16025|Vega:OTTHUMG00000182470 19 19p13.2 ELAV like RNA binding protein 1 protein-coding ELAV like RNA binding protein 1 Transgenic expression of the lincRNA-UFC1 in HCC cells promoted their proliferation and cell-cycle progression and inhibited apoptosis, whereas short hairpin RNA knockdown of lincRNA-UFC1 had opposite effects. Tumors grown from lincRNA-UFC1 knockdown were smaller than controls. The lincRNA-UFC1 interacted directly with the messenger RNA (mRNA) stabilizing protein HuR (encoded by ELAVL1) to increase levels of ¦Â-catenin mRNA (encoded by CTNNB1) and protein. Levels of lincRNA-UFC1 correlated with those of ¦Â-catenin in HCC tissues.In contrast, there was a negative correlation between levels of microRNA 34a and lincRNA-UFC1 in HCC tissues; microRNA 34a reduced the stability of lincRNA-UFC1. 489 lncRNA-BGL3 http://lncrna.com/lncrna-bgl3/ lncRNA ABL1 apoptosis down Homo sapiens myeloid leukemia 24837367 9606 25 ABL|JTK7|bcr/abl|c-ABL|c-ABL1|p150|v-abl HGNC:76|MIM:189980|Ensembl:ENSG00000097007|HPRD:01809|Vega:OTTHUMG00000020813 9 9q34.1 ABL proto-oncogene 1, non-receptor tyrosine kinase protein-coding ABL proto-oncogene 1, non-receptor tyrosine kinase Ectopic expression of lncRNA-BGL3 sensitized leukemic cells to undergo apoptosis and inhibited Bcr-Abl-induced tumorigenesis. 490 lncRNA-BGL3 http://lncrna.com/lncrna-bgl3/ lncRNA BCR apoptosis down Homo sapiens myeloid leukemia 24837367 9606 613 ALL|BCR1|CML|D22S11|D22S662|PHL HGNC:1014|MIM:151410|Ensembl:ENSG00000186716|HPRD:01044|Vega:OTTHUMG00000150655 22 22q11.23 breakpoint cluster region protein-coding breakpoint cluster region Ectopic expression of lncRNA-BGL3 sensitized leukemic cells to undergo apoptosis and inhibited Bcr-Abl-induced tumorigenesis. 491 lncRNA-LET http://lncrna.com/lncrna-let/ lncRNA apoptosis Homo sapiens 25213660 9606 The ectopic expression of lncRNA-LET led to the promotion of cell cycle arrest at G0/G1 phase and to the induction of apoptosis under hypoxic conditions. 492 lncRNA-p21 http://lncrna.com/lincRNA-p21/ lncRNA apoptosis up Homo sapiens HeLa and caspase-3-deficient MCF-7 cell 22487937 9606 Our results reveal that basal RNA expression levels as well as the changes in the lncRNA expression rates during genotoxic stress-induced apoptosis were cell-type and/or DNA-damaging agent-specific. Generally, we found that some of the RNA molecules (HOTAIR and MALAT1) are down-regulated while many of them (lincRNA-p21, GAS5, MEG3, ANRIL, and ncRNA-CCND1) are up-regulated and some others (TUG1, UCA1, and PANDA) not affected. 493 Loc554202 lncRNA apoptosis Homo sapiens breast cancer cell 24631686 9606 Moreover, knockdown of Loc554202 decreased breast cancer cell proliferation, induced apoptosis and inhibits migration/invasion in vitro and impeded tumorigenesis in vivo. These data suggest an important role of Loc554202 in breast tumorigenesis. 494 lust http://www.lncrnadb.org/Detail.aspx?TKeyID=146 lncRNA RBM5 apoptosis Homo sapiens 19559772 9606 10181 G15|LUCA15|RMB5 HGNC:9902|MIM:606884|Ensembl:ENSG00000003756|HPRD:06052|Vega:OTTHUMG00000156785 3 3p21.3 RNA binding motif protein 5 protein-coding RNA binding motif protein 5 RNA-binding protein 5; pu LUST is a novel, functional, non-coding RNA that plays a role in determining the apoptotic fate of a cell by regulating the expression of RBM5 splice variants. 495 MALAT1 http://www.lncrnadb.org/Malat1/ lncRNA BAX apoptosis up Homo sapiens cervical cancer cells 20937273 9606 581 BCL2L4 HGNC:959|MIM:600040|Ensembl:ENSG00000087088|HPRD:02498|Vega:OTTHUMG00000160476 19 19q13.3-q13.4 BCL2-associated X protein protein-coding BCL2-associated X protein BCL2-associated X protein MALAT1 supports proliferation and invasion of cervical cancer cells and knockdown of MALAT1 in CaSki cells led to an upregulation of caspase-8 and -3 and Bax and the downregulation of Bcl-2 and Bcl-xL.Thus, both studies find a plethora of potential MALAT1 functions linked to proliferation, apoptosis, migration or gene regulation and future studies will have to unravel the specificity of these effects. 496 MALAT1 http://www.lncrnadb.org/Malat1/ lncRNA BCL2 apoptosis down Homo sapiens cervical cancer cells 20937273 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 apoptosis regulator Bcl-2 MALAT1 supports proliferation and invasion of cervical cancer cells and knockdown of MALAT1 in CaSki cells led to an upregulation of caspase-8 and -3 and Bax and the downregulation of Bcl-2 and Bcl-xL.Thus, both studies find a plethora of potential MALAT1 functions linked to proliferation, apoptosis, migration or gene regulation and future studies will have to unravel the specificity of these effects. 497 MALAT1 http://www.lncrnadb.org/Malat1/ lncRNA BCL2 apoptosis Homo sapiens non-small-cell lung cancer cell 25036876 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 Bcl-2 expression was specifically associated with superior prognosis in localized NSCLC. An interaction of Bcl-2 with MALAT-1 lncRNA expression was revealed, which merits further investigation for risk prediction in resectable NSCLC patients 498 MALAT1 http://www.lncrnadb.org/Malat1/ lncRNA BCL2L1 apoptosis down Homo sapiens cervical cancer cells 20937273 9606 598 BCL-XL/S|BCL2L|BCLX|BCLXL|BCLXS|Bcl-X|PPP1R52|bcl-xL|bcl-xS HGNC:992|MIM:600039|Ensembl:ENSG00000171552|HPRD:02497|Vega:OTTHUMG00000032192 20 20q11.21 BCL2-like 1 protein-coding BCL2-like 1 apoptosis regulator Bcl-X MALAT1 supports proliferation and invasion of cervical cancer cells and knockdown of MALAT1 in CaSki cells led to an upregulation of caspase-8 and -3 and Bax and the downregulation of Bcl-2 and Bcl-xL.Thus, both studies find a plethora of potential MALAT1 functions linked to proliferation, apoptosis, migration or gene regulation and future studies will have to unravel the specificity of these effects. 499 MALAT1 http://www.lncrnadb.org/Malat1/ lncRNA CASP3 apoptosis up Homo sapiens cervical cancer cells 20937273 9606 836 CPP32|CPP32B|SCA-1 HGNC:1504|MIM:600636|Ensembl:ENSG00000164305|HPRD:02799|Vega:OTTHUMG00000133681 4 4q34 caspase 3, apoptosis-related cysteine peptidase protein-coding caspase 3, apoptosis-related cysteine peptidase CASP-3|CPP-32|PARP cleava MALAT1 supports proliferation and invasion of cervical cancer cells and knockdown of MALAT1 in CaSki cells led to an upregulation of caspase-8 and -3 and Bax and the downregulation of Bcl-2 and Bcl-xL.Thus, both studies find a plethora of potential MALAT1 functions linked to proliferation, apoptosis, migration or gene regulation and future studies will have to unravel the specificity of these effects. 500 MALAT1 http://www.lncrnadb.org/Malat1/ lncRNA CASP8 apoptosis up Homo sapiens cervical cancer cells 20937273 9606 841 ALPS2B|CAP4|Casp-8|FLICE|MACH|MCH5 HGNC:1509|MIM:601763|Ensembl:ENSG00000064012|HPRD:03459|Vega:OTTHUMG00000132821 2 2q33-q34 caspase 8, apoptosis-related cysteine peptidase protein-coding caspase 8, apoptosis-related cysteine peptidase FADD-homologous ICE/CED-3 MALAT1 supports proliferation and invasion of cervical cancer cells and knockdown of MALAT1 in CaSki cells led to an upregulation of caspase-8 and -3 and Bax and the downregulation of Bcl-2 and Bcl-xL.Thus, both studies find a plethora of potential MALAT1 functions linked to proliferation, apoptosis, migration or gene regulation and future studies will have to unravel the specificity of these effects. 501 MALAT1 http://www.lncrnadb.org/Malat1/ lncRNA CDH1 apoptosis up Homo sapiens renal cell carcinoma 25600645 9606 999 Arc-1|CD324|CDHE|ECAD|LCAM|UVO HGNC:1748|MIM:192090|Ensembl:ENSG00000039068|HPRD:01885|Vega:OTTHUMG00000137561 16 16q22.1 cadherin 1, type 1, E-cadherin (epithelial) protein-coding cadherin 1, type 1, E-cadherin (epithelial) Mechanistic investigations showed that MALAT1 was transcriptionally activated by c-Fos and that it interacted with Ezh2. After MALAT1 silencing, E-cadherin expression was increased, whereas ¦Â-catenin expression was decreased through Ezh2. Reciprocal interaction between MALAT1 and miR-205 was also observed. 502 MALAT1 http://www.lncrnadb.org/Malat1/ lncRNA CTNNB1 apoptosis down Homo sapiens renal cell carcinoma 25600645 9606 1499 CTNNB|MRD19|armadillo HGNC:2514|MIM:116806|Ensembl:ENSG00000168036|HPRD:00286|Vega:OTTHUMG00000131393 3 3p21 catenin (cadherin-associated protein), beta 1, 88kDa protein-coding catenin (cadherin-associated protein), beta 1, 88kDa Mechanistic investigations showed that MALAT1 was transcriptionally activated by c-Fos and that it interacted with Ezh2. After MALAT1 silencing, E-cadherin expression was increased, whereas ¦Â-catenin expression was decreased through Ezh2. Reciprocal interaction between MALAT1 and miR-205 was also observed. 503 MALAT1 http://www.lncrnadb.org/Malat1/ lncRNA EZH2 apoptosis Homo sapiens renal cell carcinoma 25600645 9606 2146 ENX-1|ENX1|EZH1|EZH2b|KMT6|KMT6A|WVS|WVS2 HGNC:3527|MIM:601573|Ensembl:ENSG00000106462|HPRD:03342|Vega:OTTHUMG00000158973 7 7q35-q36 enhancer of zeste 2 polycomb repressive complex 2 subunit protein-coding enhancer of zeste 2 polycomb repressive complex 2 subunit Mechanistic investigations showed that MALAT1 was transcriptionally activated by c-Fos and that it interacted with Ezh2. After MALAT1 silencing, E-cadherin expression was increased, whereas ¦Â-catenin expression was decreased through Ezh2. Reciprocal interaction between MALAT1 and miR-205 was also observed. 504 MALAT1 http://www.lncrnadb.org/Malat1/ lncRNA FOS apoptosis Homo sapiens renal cell carcinoma 25600645 9606 2353 AP-1|C-FOS|p55 HGNC:3796|MIM:164810|Ensembl:ENSG00000170345|HPRD:01275|Vega:OTTHUMG00000171774 14 14q24.3 FBJ murine osteosarcoma viral oncogene homolog protein-coding FBJ murine osteosarcoma viral oncogene homolog Mechanistic investigations showed that MALAT1 was transcriptionally activated by c-Fos and that it interacted with Ezh2. After MALAT1 silencing, E-cadherin expression was increased, whereas ¦Â-catenin expression was decreased through Ezh2. Reciprocal interaction between MALAT1 and miR-205 was also observed. 505 MALAT1 http://www.lncrnadb.org/Malat1/ lncRNA PCDH10 apoptosis down Homo sapiens endometrioid endometrial carcinoma 25085246 9606 57575 OL-PCDH|PCDH19 HGNC:13404|MIM:608286|HPRD:12204 4 4q28.3 protocadherin 10 protein-coding protocadherin 10 Restoring PCDH10 levels suppressed cell growth and triggered apoptosis in EEC cells and tumor xenografts.We found that MALAT1 transcription was regulated by Wnt/¦Â-catenin signaling via TCF promoter binding and PCDH10 decreased MALAT1 by modulating this pathway. 506 MALAT1 http://www.lncrnadb.org/Malat1/ lncRNA PTBP2 apoptosis Homo sapiens osteosarcoma cell 25592968 9606 58155 PTBLP|brPTB|nPTB HGNC:17662|MIM:608449|Ensembl:ENSG00000117569|HPRD:12233|Vega:OTTHUMG00000010685 1 1p21.3 polypyrimidine tract binding protein 2 protein-coding polypyrimidine tract binding protein 2 Consistent with a previous study, high dose of E2 treatment dramatically downregulated expressing level of long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT-1). Downregulation of MALAT-1 promoted the combination of SFPQ/PTBP2 complex. It was also observed that the proliferation, migration, invasion, colony formation and apoptosis of OS cells were remarkably affected by high dose of E2 treatment, but not by low dose, in an ER¦Á independent manner. 507 MALAT1 http://www.lncrnadb.org/Malat1/ lncRNA SFPQ apoptosis Homo sapiens osteosarcoma cell 25592968 9606 654780 - - 16 16q24.1 splicing factor proline/glutamine-rich ncRNA - Consistent with a previous study, high dose of E2 treatment dramatically downregulated expressing level of long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT-1). Downregulation of MALAT-1 promoted the combination of SFPQ/PTBP2 complex. It was also observed that the proliferation, migration, invasion, colony formation and apoptosis of OS cells were remarkably affected by high dose of E2 treatment, but not by low dose, in an ER¦Á independent manner. 508 MALAT1 http://www.lncrnadb.org/Malat1/ lncRNA apoptosis Homo sapiens hepatocellular carcinoma cells 21678027 9606 Inhibition of MALAT1 in HepG2 cells could effectively reduce cell viability, motility, invasiveness, and increase the sensitivity to apoptosis. 509 MALAT1 http://www.lncrnadb.org/Malat1/ lncRNA apoptosis down Homo sapiens breast cancer cells 22487937 9606 Our results reveal that basal RNA expression levels as well as the changes in the lncRNA expression rates during genotoxic stress-induced apoptosis were cell-type and/or DNA-damaging agent-specific. Generally, we found that some of the RNA molecules (HOTAIR and MALAT1) are down-regulated while many of them (lincRNA-p21, GAS5, MEG3, ANRIL, and ncRNA-CCND1) are up-regulated and some others (TUG1, UCA1, and PANDA) not affected. 510 MALAT1 http://www.lncrnadb.org/Malat1/ lncRNA apoptosis down Homo sapiens laryngeal squamous cell carcinoma cells 23104528 9606 The apoptosis cells were increased in MALAT-1 siRNA lentivirus-treated LSCC xenografts than the control. 511 MALAT1 http://www.lncrnadb.org/Malat1/ lncRNA apoptosis Homo sapiens bladder 23153939 9606 Cell proliferation inhibition, increased apoptosis, and decreased motility were observed in MALAT1 small interfering RNA-transfected bladder urothelial carcinoma T24 and 5637 cells. 512 MALAT1 http://www.lncrnadb.org/Malat1/ lncRNA apoptosis Homo sapiens pancreatic cancer 25269958 9606 Consistently, higher expression level of MALAT-1 was found in all seven pancreatic cancer cell lines relative to the human pancreatic ductal epithelial cell. Further function analysis revealed that downregulation of MALAT-1 could inhibit tumor cell proliferation and decrease cell migration and invasion in vitro. The underlying mechanisms are possibly involved in inducing G2/M cell cycle arrest, promoting cell apoptosis, suppressing epithelial-mesenchymal transition and reducing cancer stem-like properties. In conclusion, this study indicated that MALAT-1 may serve as an oncogenic lncRNA that is involved in malignancy phenotypes of pancreatic cancer. Therefore, it may be used as a potential therapeutic target. 513 mdm2-as http://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=6973 lncRNA AR apoptosis down Homo sapiens prostate cancer cells 19010821 9606 367 AIS|DHTR|HUMARA|HYSP1|KD|NR3C4|SBMA|SMAX1|TFM HGNC:644|MIM:313700|Ensembl:ENSG00000169083|HPRD:02437|Vega:OTTHUMG00000021740 X Xq12 androgen receptor protein-coding androgen receptor androgen nuclear receptor In this study, the effect of Ad-E2F1 and AS-MDM2 in combination with radiation was investigated in three prostate cancer cell lines: LNCaP cells, LNCaP-Res cells [androgen insensitive with functional p53 and androgen receptor (AR)], and PC3 cells (androgen insensitive, p53(null), and AR(null)). A supra-additive radiosensitizing effect was observed in terms of clonogenic inhibition and induction of apoptosis (caspase-3 + caspase-7 activity) in response to Ad-E2F1 plus AS-MDM2 treatments in all three cell lines. In LNCaP and LNCaP-Res, these combination treatments elevated the levels of phospho-Ser(15) p53 with significant induction of p21(waf1/cip1), phospho-gammaH2AX, PUMA, and Bax levels and reduction of AR and bcl-2 expression. 514 mdm2-as http://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=6973 lncRNA BAX apoptosis up Homo sapiens prostate cancer cells 19010821 9606 581 BCL2L4 HGNC:959|MIM:600040|Ensembl:ENSG00000087088|HPRD:02498|Vega:OTTHUMG00000160476 19 19q13.3-q13.4 BCL2-associated X protein protein-coding BCL2-associated X protein BCL2-associated X protein In this study, the effect of Ad-E2F1 and AS-MDM2 in combination with radiation was investigated in three prostate cancer cell lines: LNCaP cells, LNCaP-Res cells [androgen insensitive with functional p53 and androgen receptor (AR)], and PC3 cells (androgen insensitive, p53(null), and AR(null)). A supra-additive radiosensitizing effect was observed in terms of clonogenic inhibition and induction of apoptosis (caspase-3 + caspase-7 activity) in response to Ad-E2F1 plus AS-MDM2 treatments in all three cell lines. In LNCaP and LNCaP-Res, these combination treatments elevated the levels of phospho-Ser(15) p53 with significant induction of p21(waf1/cip1), phospho-gammaH2AX, PUMA, and Bax levels and reduction of AR and bcl-2 expression. 515 mdm2-as http://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=6973 lncRNA BBC3 apoptosis up Homo sapiens prostate cancer cells 19010821 9606 27113 JFY-1|JFY1|PUMA HGNC:17868|MIM:605854|Ensembl:ENSG00000105327|HPRD:16165|Vega:OTTHUMG00000183489 19 19q13.3-q13.4 BCL2 binding component 3 protein-coding BCL2 binding component 3 bcl-2-binding component 3 In this study, the effect of Ad-E2F1 and AS-MDM2 in combination with radiation was investigated in three prostate cancer cell lines: LNCaP cells, LNCaP-Res cells [androgen insensitive with functional p53 and androgen receptor (AR)], and PC3 cells (androgen insensitive, p53(null), and AR(null)). A supra-additive radiosensitizing effect was observed in terms of clonogenic inhibition and induction of apoptosis (caspase-3 + caspase-7 activity) in response to Ad-E2F1 plus AS-MDM2 treatments in all three cell lines. In LNCaP and LNCaP-Res, these combination treatments elevated the levels of phospho-Ser(15) p53 with significant induction of p21(waf1/cip1), phospho-gammaH2AX, PUMA, and Bax levels and reduction of AR and bcl-2 expression. 516 mdm2-as http://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=6973 lncRNA BCL2 apoptosis down Homo sapiens prostate cancer cells 19010821 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 apoptosis regulator Bcl-2 In this study, the effect of Ad-E2F1 and AS-MDM2 in combination with radiation was investigated in three prostate cancer cell lines: LNCaP cells, LNCaP-Res cells [androgen insensitive with functional p53 and androgen receptor (AR)], and PC3 cells (androgen insensitive, p53(null), and AR(null)). A supra-additive radiosensitizing effect was observed in terms of clonogenic inhibition and induction of apoptosis (caspase-3 + caspase-7 activity) in response to Ad-E2F1 plus AS-MDM2 treatments in all three cell lines. In LNCaP and LNCaP-Res, these combination treatments elevated the levels of phospho-Ser(15) p53 with significant induction of p21(waf1/cip1), phospho-gammaH2AX, PUMA, and Bax levels and reduction of AR and bcl-2 expression. 517 mdm2-as http://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=6973 lncRNA CDKN1A apoptosis up Homo sapiens prostate cancer cells 19010821 9606 1026 CAP20|CDKN1|CIP1|MDA-6|P21|SDI1|WAF1|p21CIP1 HGNC:1784|MIM:116899|Ensembl:ENSG00000124762|HPRD:00298|Vega:OTTHUMG00000014603 6 6p21.2 cyclin-dependent kinase inhibitor 1A (p21, Cip1) protein-coding cyclin-dependent kinase inhibitor 1A (p21, Cip1) CDK-interacting protein 1 In this study, the effect of Ad-E2F1 and AS-MDM2 in combination with radiation was investigated in three prostate cancer cell lines: LNCaP cells, LNCaP-Res cells [androgen insensitive with functional p53 and androgen receptor (AR)], and PC3 cells (androgen insensitive, p53(null), and AR(null)). A supra-additive radiosensitizing effect was observed in terms of clonogenic inhibition and induction of apoptosis (caspase-3 + caspase-7 activity) in response to Ad-E2F1 plus AS-MDM2 treatments in all three cell lines. In LNCaP and LNCaP-Res, these combination treatments elevated the levels of phospho-Ser(15) p53 with significant induction of p21(waf1/cip1), phospho-gammaH2AX, PUMA, and Bax levels and reduction of AR and bcl-2 expression. 518 MEG3 http://lncrna.com/MEG3/ lncRNA BAX apoptosis Homo sapiens HTR-8/SVneo and JEG4 cells 25358633 9606 581 BCL2L4 HGNC:959|MIM:600040|Ensembl:ENSG00000087088|HPRD:02498|Vega:OTTHUMG00000160476 19 19q13.3-q13.4 BCL2-associated X protein protein-coding BCL2-associated X protein Over-expression of MEG3 reduced apoptosis and promoted migration of HTR-8/SVneo and JEG3 cells. Furthermore, inhibition of endogenous MEG3 increased apoptosis and decreased migration of HTR-8/SVneo and JEG3 cells. Additionally, lncRNA MEG3 influenced expression of NF-¦ÊB, Caspase-3, and Bax protein expressions in trophoblast cells. 519 MEG3 http://lncrna.com/MEG3/ lncRNA CASP3 apoptosis Homo sapiens HTR-8/SVneo and JEG3 cells 25358633 9606 836 CPP32|CPP32B|SCA-1 HGNC:1504|MIM:600636|Ensembl:ENSG00000164305|HPRD:02799|Vega:OTTHUMG00000133681 4 4q34 caspase 3, apoptosis-related cysteine peptidase protein-coding caspase 3, apoptosis-related cysteine peptidase Over-expression of MEG3 reduced apoptosis and promoted migration of HTR-8/SVneo and JEG3 cells. Furthermore, inhibition of endogenous MEG3 increased apoptosis and decreased migration of HTR-8/SVneo and JEG3 cells. Additionally, lncRNA MEG3 influenced expression of NF-¦ÊB, Caspase-3, and Bax protein expressions in trophoblast cells. 520 MEG3 http://lncrna.com/MEG3/ lncRNA MDM2 apoptosis Homo sapiens lung 24098911 9606 4193 ACTFS|HDMX|hdm2 HGNC:6973|MIM:164785|Ensembl:ENSG00000135679|HPRD:01272|Vega:OTTHUMG00000142827 12 12q14.3-q15 MDM2 proto-oncogene, E3 ubiquitin protein ligase protein-coding MDM2 proto-oncogene, E3 ubiquitin protein ligase Overexpression of MEG3 decreased NSCLC cells proliferation and induced apoptosis in vitro and impeded tumorigenesis in vivo. MDM2 and p53 protein levels were affected by MEG3 over-expression in vitro. 521 MEG3 http://lncrna.com/MEG3/ lncRNA TAB1 apoptosis Homo sapiens hepatic stellate 25201080 9606 10454 3'-Tab1|MAP3K7IP1 HGNC:18157|MIM:602615|Ensembl:ENSG00000100324|HPRD:04012|Vega:OTTHUMG00000151102 22 22q13.1 TGF-beta activated kinase 1/MAP3K7 binding protein 1 protein-coding TGF-beta activated kinase 1/MAP3K7 binding protein 1 Expression of MEG3 was downregulated in human hepatic stellate cell lines LX-2 cells in response to transforming growth factor-¦Â1 (TGF-¦Â1) stimulation in dose and time-dependent manner. Enforced expression of MEG3 in LX-2 cells inhibited TGF-¦Â1-induced cell proliferation, while promoting cell apoptosis. 522 MEG3 http://lncrna.com/MEG3/ lncRNA TP53 apoptosis up Homo sapiens glioma cells 22234798 9606 7157 BCC7|LFS1|P53|TRP53 HGNC:11998|MIM:191170|Ensembl:ENSG00000141510|HPRD:01859|Vega:OTTHUMG00000162125 17 17p13.1 tumor protein p53 protein-coding tumor protein p53 antigen NY-CO-13; cellula Ectopic expression of MEG3 inhibited cell proliferation and promoted cell apoptosis in U251 and U87 MG human glioma cell lines. 523 MEG3 http://lncrna.com/MEG3/ lncRNA TP53 apoptosis up Homo sapiens breast cancer cells 22393162 9606 7157 BCC7|LFS1|P53|TRP53 HGNC:11998|MIM:191170|Ensembl:ENSG00000141510|HPRD:01859|Vega:OTTHUMG00000162125 17 17p13.1 tumor protein p53 protein-coding tumor protein p53 antigen NY-CO-13; cellula Re-expression of MEG3 inhibits tumor cell proliferation in culture and colony formation in soft agar.This growth inhibition is partly the result of apoptosis induced by meg3. 524 MEG3 http://lncrna.com/MEG3/ lncRNA TP53 apoptosis Homo sapiens gastric 24006224 9606 7157 BCC7|LFS1|P53|TRP53 HGNC:11998|MIM:191170|Ensembl:ENSG00000141510|HPRD:01859|Vega:OTTHUMG00000162125 17 17p13.1 tumor protein p53 protein-coding tumor protein p53 Furthermore, knockdown of MEG3 expression by siRNA could promote cell proliferation, while ectopic expression of MEG3 inhibited cell proliferation, promoted cell apoptosis, and modulated p53 expression in gastric cancer cell lines. 525 MEG3 http://lncrna.com/MEG3/ lncRNA TP53 apoptosis Homo sapiens lung 24098911 9606 7157 BCC7|LFS1|P53|TRP53 HGNC:11998|MIM:191170|Ensembl:ENSG00000141510|HPRD:01859|Vega:OTTHUMG00000162125 17 17p13.1 tumor protein p53 protein-coding tumor protein p53 Overexpression of MEG3 decreased NSCLC cells proliferation and induced apoptosis in vitro and impeded tumorigenesis in vivo. MDM2 and p53 protein levels were affected by MEG3 over-expression in vitro. 526 MEG3 http://lncrna.com/MEG3/ lncRNA TP53 apoptosis up Homo sapiens ovarian 24859196 9606 7157 BCC7|LFS1|P53|TRP53 HGNC:11998|MIM:191170|Ensembl:ENSG00000141510|HPRD:01859|Vega:OTTHUMG00000162125 17 17p13.1 tumor protein p53 protein-coding tumor protein p53 In addition, ectopic expression of MEG3 suppressed the proliferation and growth of OVCAR3 cells and promoted apoptosis. Finally, MEG3 activated p53 in OVCAR3 cells. 527 MEG3 http://lncrna.com/MEG3/ lncRNA TP53 apoptosis up Homo sapiens 25201080 9606 7157 BCC7|LFS1|P53|TRP53 HGNC:11998|MIM:191170|Ensembl:ENSG00000141510|HPRD:01859|Vega:OTTHUMG00000162125 17 17p13.1 tumor protein p53 protein-coding tumor protein p53 More importantly, overexpression of MEG3 could activate p53 and mediate cytochrome crelease, subsequently leading to caspase-3-dependent apoptosis in TGF-¦Â1-treated LX-2 cells. 528 MEG3 http://lncrna.com/MEG3/ lncRNA TP53 apoptosis up Homo sapiens hepatocellular carcinoma 25641194 9606 7157 BCC7|LFS1|P53|TRP53 HGNC:11998|MIM:191170|Ensembl:ENSG00000141510|HPRD:01859|Vega:OTTHUMG00000162125 17 17p13.1 tumor protein p53 protein-coding tumor protein p53 The inhibition affection in proliferation and inducing affection in apoptosis was further confirmed in vivo and vitro, we also demonstrated that MEG3 regulates HCC cell proliferation and apoptosis partially via the accumulation of p53. Besides, the hypermethylation of MEG3 in promoter region was identified by bisulfite sequencing while MEG3 increased with the inhibition of methylation. Subsequently, UHRF1, a new identified oncogene which is required for DNA methylation and recruits, was investigated. A negative correlation of MEG3 and UHRF1 expression was verified in primary HCC tissues. Down-regulation of UHRF1 induced MEG3 expression in HCC cell lines, which could be reversed by the up-regulation of UHRF1. 529 MEG3 http://lncrna.com/MEG3/ lncRNA UHRF1 apoptosis Homo sapiens hepatocellular carcinoma 25641194 9606 29128 ICBP90|Np95|RNF106|hNP95|hUHRF1|huNp95 HGNC:12556|MIM:607990|HPRD:06992 19 19p13.3 ubiquitin-like with PHD and ring finger domains 1 protein-coding ubiquitin-like with PHD and ring finger domains 1 The inhibition affection in proliferation and inducing affection in apoptosis was further confirmed in vivo and vitro, we also demonstrated that MEG3 regulates HCC cell proliferation and apoptosis partially via the accumulation of p53. Besides, the hypermethylation of MEG3 in promoter region was identified by bisulfite sequencing while MEG3 increased with the inhibition of methylation. Subsequently, UHRF1, a new identified oncogene which is required for DNA methylation and recruits, was investigated. A negative correlation of MEG3 and UHRF1 expression was verified in primary HCC tissues. Down-regulation of UHRF1 induced MEG3 expression in HCC cell lines, which could be reversed by the up-regulation of UHRF1. 530 MEG3 http://lncrna.com/MEG3/ lncRNA apoptosis Homo sapiens hepatocellular cancer cells 21625215 9606 Enforced expression of MEG3 in HCC cells significantly decreased both anchorage-dependent and -independent cell growth, and induced apoptosis. 531 MEG3 http://lncrna.com/MEG3/ lncRNA apoptosis up Homo sapiens breast cancer cells 22487937 9606 Our results reveal that basal RNA expression levels as well as the changes in the lncRNA expression rates during genotoxic stress-induced apoptosis were cell-type and/or DNA-damaging agent-specific. Generally, we found that some of the RNA molecules (HOTAIR and MALAT1) are down-regulated while many of them (lincRNA-p21, GAS5, MEG3, ANRIL, and ncRNA-CCND1) are up-regulated and some others (TUG1, UCA1, and PANDA) not affected. 532 MEG3 http://lncrna.com/MEG3/ lncRNA apoptosis up Homo sapiens bladder cancer cells 23295831 9606 A significant negative correlation was observed between MEG3 levels and LC3-II (autophagy marker) levels in vivo. We further demonstrated that MEG3 markedly suppressed autophagy activation, whereas MEG3 knockdown activated autophagy in human bladder cancer cell lines. 533 MEG3 http://lncrna.com/MEG3/ lncRNA apoptosis Homo sapiens cervical carcinoma 23790166 9606 Further investigation into the mechanisms responsible for the growth inhibitory effects revealed that overexpression of MEG3 resulted in the induction of G2/M cell cycle arrest and apoptosis. 534 miR-642 hsa-miR-642a-5p,hsa-miR-642b-3p,hsa-miR-642a-3p,hsa-miR-642b-5p MIMAT0003312,MIMAT0018444,MIMAT0020924,MIMAT0022736 lncRNA KRT19 apoptosis down Homo sapiens hepatocellular carcinoma cell 25476897 9606 3880 CK19|K19|K1CS HGNC:6436|MIM:148020|Ensembl:ENSG00000171345|HPRD:01007|Vega:OTTHUMG00000133422 17 17q21.2 keratin 19 protein-coding keratin 19 Knockdown of Linc00974 resulted in an inhibition of cell proliferation and invasion with an activation of apoptosis and cell cycle arrest in vitro, which was also validated by a subcutaneous and tail vein/intraperitoneal injection xenotransplantation model in vivo. We further investigated the interaction pattern of Linc00974 and KRT19. MiR-642 was identified, by acting as the competing endogenous RNA in regulating Linc00974 and KRT19. Linc00974 was increased owing to an abnormal hypomethylation promoter, which induced the upregulation of KRT19 via ceRNA interaction, resulting in the activation of the Notch and TGF-¦Â pathways as detected by cDNA microarray. 535 miR-642 hsa-miR-642a-5p,hsa-miR-642b-3p,hsa-miR-642a-3p,hsa-miR-642b-5p MIMAT0003312,MIMAT0018444,MIMAT0020924,MIMAT0022736 lncRNA LINC00974 apoptosis Homo sapiens hepatocellular carcinoma cell 25476897 9606 147093 - HGNC:27105|Ensembl:ENSG00000226629 17 17q21.31 long intergenic non-protein coding RNA 974 ncRNA long intergenic non-protein coding RNA 974 Knockdown of Linc00974 resulted in an inhibition of cell proliferation and invasion with an activation of apoptosis and cell cycle arrest in vitro, which was also validated by a subcutaneous and tail vein/intraperitoneal injection xenotransplantation model in vivo. We further investigated the interaction pattern of Linc00974 and KRT19. MiR-642 was identified, by acting as the competing endogenous RNA in regulating Linc00974 and KRT19. Linc00974 was increased owing to an abnormal hypomethylation promoter, which induced the upregulation of KRT19 via ceRNA interaction, resulting in the activation of the Notch and TGF-¦Â pathways as detected by cDNA microarray. 536 MRUL lncRNA ABCB1 apoptosis Homo sapiens gastric cancer cell 24958102 9606 5243 ABC20|CD243|CLCS|GP170|MDR1|P-GP|PGY1 HGNC:40|MIM:171050|Ensembl:ENSG00000085563|HPRD:01370|Vega:OTTHUMG00000023393 7 7q21.12 ATP-binding cassette, sub-family B (MDR/TAP), member 1 protein-coding ATP-binding cassette, sub-family B (MDR/TAP), member 1 We show here that the lncRNA MRUL (MDR-related and upregulated lncRNA), located 400 kb downstream of ABCB1 (ATP-binding cassette, subfamily B, member 1), was significantly upregulated in two multidrug-resistant GC cell sublines, SGC7901/ADR and SGC7901/VCR. MRUL knockdown in SGC7901/ADR and SGC7901/VCR cells led to increased rates of apoptosis, increased accumulation, and reduced doxorubicin (Adriamycin [ADR]) release in the presence of ADR or vincristine. Moreover, MRUL depletion reduced ABCB1 mRNA levels in a dose- and time-dependent manner. Heterologous luciferase reporter assays demonstrated that MRUL might positively affect ABCB1 expression in an orientation- and position-independent manner. 537 ncRNA-CCND1 http://www.lncrnadb.org/p53mrna/ lncRNA apoptosis up Homo sapiens HeLa and caspase-3-deficient MCF-7 cell 22487937 9606 Our results reveal that basal RNA expression levels as well as the changes in the lncRNA expression rates during genotoxic stress-induced apoptosis were cell-type and/or DNA-damaging agent-specific. Generally, we found that some of the RNA molecules (HOTAIR and MALAT1) are down-regulated while many of them (lincRNA-p21, GAS5, MEG3, ANRIL, and ncRNA-CCND1) are up-regulated and some others (TUG1, UCA1, and PANDA) not affected. 538 NEAT1 lncRNA EPAS1 apoptosis down Homo sapiens breast 25417700 9606 2034 ECYT4|HIF2A|HLF|MOP2|PASD2|bHLHe73 HGNC:3374|MIM:603349|Ensembl:ENSG00000116016|HPRD:06787|Vega:OTTHUMG00000128818 2 2p21-p16 endothelial PAS domain protein 1 protein-coding endothelial PAS domain protein 1 Here, we show that NEAT1 long non-coding RNA (lncRNA) is a direct transcriptional target of HIF in many breast cancer cell lines and in solid tumors. Unlike previously described lncRNAs, NEAT1 is regulated principally by HIF-2 rather than by HIF-1. Induction of NEAT1 in hypoxia also leads to accelerated cellular proliferation, improved clonogenic survival and reduced apoptosis, all of which are hallmarks of increased tumorigenesis. 539 Ntab http://www.valadkhanlab.org/web/cgi-bin/output_1.cgi?name=Ntab&genome= lncRNA SLC1A2 apoptosis up Homo sapiens central nervous system 21110225 9606 6506 EAAT2|GLT-1 HGNC:10940|MIM:600300|Ensembl:ENSG00000110436|HPRD:02625|Vega:OTTHUMG00000044391 11 11p13-p12 solute carrier family 1 (glial high affinity glutamate transporter), member 2 protein-coding solute carrier family 1 (glial high affinity glutamate transporter), member 2 excitatory amino acid tr Fragments of Ntab act as enhancers of EAAT2/GLT-1 transcription. Expression of EAAT2/GLT-1 is perturbed in various acute and chronic brain diseases eventually allowing for the onset of neurotoxic extracellular glutamate concentrations and subsequent excitotoxic neuronal cell death. 540 p53-mRNA http://www.lncrnadb.org/p53mrna/ lncRNA HTATIP2 apoptosis Homo sapiens hepatocellular carcinoma cell 18519672 9606 10553 CC3|SDR44U1|TIP30 HGNC:16637|MIM:605628|Ensembl:ENSG00000109854|HPRD:09288|Vega:OTTHUMG00000166015 11 11p15.1 HIV-1 Tat interactive protein 2, 30kDa protein-coding HIV-1 Tat interactive protein 2, 30kDa Tip30 is involved in cellular oxidative stress surveillance and induces apoptosis through stabilization of p53 mrna in hcc cells. 541 p53-mRNA http://www.lncrnadb.org/p53mrna/ lncRNA PITX1 apoptosis Homo sapiens mammary carcinoma cells 17762884 9606 5307 BFT|CCF|LBNBG|POTX|PTX1 HGNC:9004|MIM:602149|Ensembl:ENSG00000069011|HPRD:03688|Vega:OTTHUMG00000149983 5 5q31.1 paired-like homeodomain 1 protein-coding paired-like homeodomain 1 Increased p53 mrna expression was due to activation of the p53 promoter by hPitx1. Forced expression of hpitx1 resulted in cell-cycle arrest and p53-dependent apoptosis in p53-replete MCF-7 cells. Furthermore, hPitx1 stimulated the transcription of p53 target genes involved in cell-cycle arrest and apoptosis (p21 and ptgf-beta), again in a p53-dependent manner.Depletion of p53 by sirna dramatically attenuated hpitx1-induced apoptosis in MCF-7 cells. 542 p53-mRNA http://www.lncrnadb.org/p53mrna/ lncRNA apoptosis Homo sapiens ovarian carcinoma cells 8895543 9606 Cisplatin-induced apoptosis and p53 gene status were analyzed in human ovarian carcinoma. A 2-fold increase in p53 mRNA and protein amounts was observed in resistant cells as assessed by Northern and Western blots, respectively. 543 p53-mRNA http://www.lncrnadb.org/p53mrna/ lncRNA apoptosis Homo sapiens immune cells 9647779 9606 Moreover, we show that HDAC inhibitor-induced apoptosis is associated with early abrogation of gamma-IFN production by Th1 lymphocytes and with p53 mRNA downregulation. 544 p53-mRNA http://www.lncrnadb.org/p53mrna/ lncRNA apoptosis Homo sapiens breast cancer cells 10705995 9606 Progesterone increased p53 mRNA levels. These results demonstrate that progesterone at relative high physiological concentrations, but comparable to those seen in plasma during the third trimester of human pregnancy, exhibited a strong antiproliferative effect on breast cancer cells and induced apoptosis. 545 PANDA http://www.lncrnadb.org/Detail.aspx?TKeyID=267 lncRNA APAF1 apoptosis down Homo sapiens fibroblasts 21642992 9606 317 APAF-1|CED4 HGNC:576|MIM:602233|Ensembl:ENSG00000120868|HPRD:03755|Vega:OTTHUMG00000170214 12 12q23 apoptotic peptidase activating factor 1 protein-coding apoptotic peptidase activating factor 1 apoptotic protease-activa PANDA depletion induced several genes encoding canonical activators of apoptosis, such as APAF1, BIK, FAS and LRDD. 546 PANDA lncRNA BCL2 apoptosis Homo sapiens lung cancer cell 25719249 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 We also showed that PANDAR-mediated growth regulation is in part due to the transcriptional modulation of Bcl-2 by interacting with NF-YA, thus affecting NSCLC cell apoptosis. Further experiments demonstrated that PANDAR expression was induced by p53, and chromatin immunoprecipitation (ChIP) assays confirmed that PANDAR was a direct transcriptional target of p53 in NSCLC cells. 547 PANDA http://www.lncrnadb.org/Detail.aspx?TKeyID=267 lncRNA BIK apoptosis down Homo sapiens fibroblasts 21642992 9606 638 BIP1|BP4|NBK HGNC:1051|MIM:603392|Ensembl:ENSG00000100290|HPRD:04547|Vega:OTTHUMG00000150703 22 22q13.31 BCL2-interacting killer (apoptosis-inducing) protein-coding BCL2-interacting killer (apoptosis-inducing) apoptosis inducer NBK; ap PANDA depletion induced several genes encoding canonical activators of apoptosis, such as APAF2, BIK, FAS and LRDD. 548 PANDA http://www.lncrnadb.org/Detail.aspx?TKeyID=267 lncRNA FAS apoptosis down Homo sapiens fibroblasts 21642992 9606 355 ALPS1A|APO-1|APT1|CD95|FAS1|FASTM|TNFRSF6 HGNC:11920|MIM:134637|Ensembl:ENSG00000026103|HPRD:00609|Vega:OTTHUMG00000018701 10 10q24.1 Fas cell surface death receptor protein-coding Fas cell surface death receptor leucine-rich repeat and d PANDA depletion induced several genes encoding canonical activators of apoptosis, such as APAF4, BIK, FAS and LRDD. 549 PANDA http://www.lncrnadb.org/Detail.aspx?TKeyID=267 lncRNA NFYA apoptosis down Homo sapiens fibroblasts 23222637 9606 4800 CBF-A|CBF-B|HAP2|NF-YA HGNC:7804|MIM:189903|HPRD:01793 6 6p21.3 nuclear transcription factor Y, alpha protein-coding nuclear transcription factor Y, alpha bcl-2-binding component 3 The depletion of PANDA substantially increases the occupancy of NF-YA at pro-apoptotic target genes such as CCNB1, FAS, BBC3 (PUMA) and PMAIP3 (NOXA). 550 PANDA lncRNA NFYA apoptosis Homo sapiens lung cancer cell 25719249 9606 4800 CBF-A|CBF-B|HAP2|NF-YA HGNC:7804|MIM:189903|HPRD:01793 6 6p21.3 nuclear transcription factor Y, alpha protein-coding nuclear transcription factor Y, alpha We also showed that PANDAR-mediated growth regulation is in part due to the transcriptional modulation of Bcl-2 by interacting with NF-YA, thus affecting NSCLC cell apoptosis. Further experiments demonstrated that PANDAR expression was induced by p53, and chromatin immunoprecipitation (ChIP) assays confirmed that PANDAR was a direct transcriptional target of p53 in NSCLC cells. 551 PANDA http://www.lncrnadb.org/Detail.aspx?TKeyID=267 lncRNA PIDD1 apoptosis down Homo sapiens fibroblasts 21642992 9606 55367 LRDD|PIDD HGNC:16491|MIM:605247|Ensembl:ENSG00000177595|HPRD:11284|Vega:OTTHUMG00000133306 11 11p15.5 p53-induced death domain protein 1 protein-coding p53-induced death domain protein 1 leucine-rich repeat and d PANDA depletion induced several genes encoding canonical activators of apoptosis, such as APAF4, BIK, FAS and LRDD. 552 PANDA lncRNA RASA1 apoptosis down Homo sapiens 25501747 9606 5921 CM-AVM|CMAVM|GAP|PKWS|RASA|RASGAP|p120GAP|p120RASGAP HGNC:9871|MIM:139150|Ensembl:ENSG00000145715|HPRD:00745|Vega:OTTHUMG00000162605 5 5q13.3 RAS p21 protein activator (GTPase activating protein) 1 protein-coding RAS p21 protein activator (GTPase activating protein) 1 We also show that forced expression of oncogenic Ras increases the expression of lncRNA PANDA (p21 associated ncRNA DNA damage activated), which is involved in the regulation of apoptosis. 553 PANDA lncRNA TP53 apoptosis up Homo sapiens lung cancer cell 25719249 9606 7157 BCC7|LFS1|P53|TRP53 HGNC:11998|MIM:191170|Ensembl:ENSG00000141510|HPRD:01859|Vega:OTTHUMG00000162125 17 17p13.1 tumor protein p53 protein-coding tumor protein p53 We also showed that PANDAR-mediated growth regulation is in part due to the transcriptional modulation of Bcl-2 by interacting with NF-YA, thus affecting NSCLC cell apoptosis. Further experiments demonstrated that PANDAR expression was induced by p53, and chromatin immunoprecipitation (ChIP) assays confirmed that PANDAR was a direct transcriptional target of p53 in NSCLC cells. 554 PANDA http://www.lncrnadb.org/Detail.aspx?TKeyID=267 lncRNA apoptosis up Homo sapiens HeLa and caspase-3-deficient MCF-7 cell 22487937 9606 Our results reveal that basal RNA expression levels as well as the changes in the lncRNA expression rates during genotoxic stress-induced apoptosis were cell-type and/or DNA-damaging agent-specific. Generally, we found that some of the RNA molecules (HOTAIR and MALAT1) are down-regulated while many of them (lincRNA-p21, GAS5, MEG3, ANRIL, and ncRNA-CCND1) are up-regulated and some others (TUG1, UCA1, and PANDA) not affected. 555 pca3 http://valadkhanlab.org/web/cgi-bin/output_1.cgi?name=pca3&genome=huma lncRNA apoptosis Homo sapiens prostate adenocarcinoma cells 23130941 9606 983 CDC2|CDC28A|P34CDC2 HGNC:1722|Ensembl:ENSG00000170312|HPRD:00302|MIM:116940|Vega:OTTHUMG00000018290 10 10q21.1 cyclin-dependent kinase 1 protein coding cyclin-dependent kinase 1 cell cycle controller CDC PCA3 noncoding RNA is involved in the control of prostate-cancer cell survival and modulates androgen receptor signaling.PCA6 silencing decreases cell growth and survival and induces apoptotic cell death in prostate-cancer cells 556 PCAT-1 lncRNA apoptosis Homo sapiens prostate, Esophageal squamous cell carcinoma 25731728 9606 Prostate cancer-associated ncRNA transcript 1 (PCAT-1) is one of the lncRNAs involved in cell apoptosis and proliferation of prostate cancer. 557 pcgem1 http://www.lncrnadb.org/Detail.aspx?TKeyID=110 lncRNA CASP7 apoptosis down Homo sapiens prostate 16569192 9606 840 CASP-7|CMH-1|ICE-LAP3|LICE2|MCH3 HGNC:1508|MIM:601761|Ensembl:ENSG00000165806|HPRD:03457|Vega:OTTHUMG00000019076 10 10q25 caspase 7, apoptosis-related cysteine peptidase protein-coding caspase 7, apoptosis-related cysteine peptidase ADP-ribosyltransferase (N This study demonstrates that PCGEM1 overexpression in LNCaP cell culture model results in the inhibition of apoptosis induced by doxorubicin (DOX). Induction of p53 and p21(Waf1/Cip1) by DOX were delayed in LNCaP cells stably overexpressing PCGEM1 (LNCaP-PCGEM1 cells) compared to control LNCaP cells. The protein levels of cleaved caspase 7, and cleaved PARP were attenuated in DOXtreated LNCaP-PCGEM1 cells compared to control LNCaP cells. Similar results were observed in LNCaP cells transiently overexpressing PCGEM1. The inhibition of PARP cleavage by PCGEM1 overexpression was also observed in LNCaP-PCGEM1 cells incubated with etoposide and sodium selenite. 558 pcgem1 http://www.lncrnadb.org/Detail.aspx?TKeyID=110 lncRNA PARP1 apoptosis down Homo sapiens prostate 16569192 9606 142 ADPRT|ADPRT 1|ADPRT1|ARTD1|PARP|PARP-1|PPOL|pADPRT-1 HGNC:270|MIM:173870|Ensembl:ENSG00000143799|HPRD:01435|Vega:OTTHUMG00000037556 1 1q41-q42 poly (ADP-ribose) polymerase 1 protein-coding poly (ADP-ribose) polymerase 1 ADP-ribosyltransferase (N This study demonstrates that PCGEM1 overexpression in LNCaP cell culture model results in the inhibition of apoptosis induced by doxorubicin (DOX). Induction of p53 and p21(Waf1/Cip1) by DOX were delayed in LNCaP cells stably overexpressing PCGEM1 (LNCaP-PCGEM1 cells) compared to control LNCaP cells. The protein levels of cleaved caspase 7, and cleaved PARP were attenuated in DOXtreated LNCaP-PCGEM1 cells compared to control LNCaP cells. Similar results were observed in LNCaP cells transiently overexpressing PCGEM1. The inhibition of PARP cleavage by PCGEM1 overexpression was also observed in LNCaP-PCGEM1 cells incubated with etoposide and sodium selenite. 559 PCGEM1 lncRNA apoptosis Homo sapiens 19186008 9606 Phytosterol inhibition of PCGEM1 and cell growth and the overexpression of caveolin-1, suggests that poor disease prognosis anchors on the ability of caveolin-1 to regulate downstream oncogene(s) and apoptosis genes. 560 PlncRNA-1 http://www.ncbi.nlm.nih.gov/gene/?term=PlncRNA-1 lncRNA apoptosis Homo sapiens LNCaP and LNCaP-AI cell lines 22264502 9606 Silencing of PlncRNA-1 significantly reduced cell proliferation and induced apoptosis in CaP cell lines LNCaP and LNCaP-AI. 561 PlncRNA-1 lncRNA apoptosis Homo sapiens esophageal squamous cell 24337686 9606 PlncRNA-1 is one of lncRNAs that is associated with cell apoptosis and proliferation of prostate cancer. 562 PRNCR1 lncRNA AR apoptosis up Homo sapiens 23948400 9606 367 AIS|DHTR|HUMARA|HYSP1|KD|NR3C4|SBMA|SMAX1|TFM HGNC:644|MIM:313700|Ensembl:ENSG00000169083|HPRD:02437|Vega:OTTHUMG00000021740 X Xq12 androgen receptor protein-coding androgen receptor After transfected with PRNCR1-siRNA to silence the PRNCR1 mRNA expression, the C4-2 cells showed the inhibited expression of AR protein, the depressed proliferation and invasion abilities and the increased apoptosis rate. 563 PVT1 lncRNA MYC apoptosis down Homo sapiens malignant pleural mesothelioma 24926545 9606 4609 MRTL|MYCC|bHLHe39|c-Myc HGNC:7553|MIM:190080|Ensembl:ENSG00000136997|HPRD:01818|Vega:OTTHUMG00000128475 8 8q24.21 v-myc avian myelocytomatosis viral oncogene homolog protein-coding v-myc avian myelocytomatosis viral oncogene homolog Frequent coamplification and cooperation between C-MYC and PVT1 oncogenes promote malignant pleural mesothelioma. 564 PVT1 lncRNA apoptosis Homo sapiens breast and ovarian cancer cell lines 17908964 9606 Inhibition of PVT1 expression also induced a strong apoptotic response in cell lines in which it was overexpressed but not in lines in which it was not amplified/overexpressed. 565 PVT1 lncRNA apoptosis Homo sapiens colorectal 24196785 9606 Colorectal cancer (CRC) cells transfected with PVT-1 siRNA exhibited significant loss of their proliferation and invasion capabilities. In these cells, the TGF-¦Âsignalling pathway and apoptotic signals were significantly activated. 566 RN7SK http://www.lncrnadb.org/Detail.aspx?TKeyID=190 lncRNA apoptosis Homo sapiens cervical cancer cells 16152622 9606 SiRNA depletion of 7SK snRNA induces apoptosis but does not affect expression of the HIV-1 LTR or P-TEFb-dependent cellular genes. 567 RP11-296A18.3 lncRNA FAF1 apoptosis up Homo sapiens 25280944 9606 11124 HFAF1s|UBXD12|UBXN3A|hFAF1 HGNC:3578|MIM:604460|Ensembl:ENSG00000185104|HPRD:05124 1 1p33 Fas (TNFRSF6) associated factor 1 protein-coding Fas (TNFRSF6) associated factor 1 Interestingly, we found that Fas-associated protein factor-1 (FAF1), which potentiates the Fas-mediated apoptosis and its nearby enhancer-like lncRNA RP11-296A18.3, were highly expressed in the degenerative discs. Subsequent qRT-PCR results confirmed the changes. 568 sfRNA lncRNA IRF3 apoptosis down Homo sapiens 23755934 9606 3661 - HGNC:6118|MIM:603734|Ensembl:ENSG00000126456|HPRD:04769|Vega:OTTHUMG00000183287 19 19q13.3-q13.4 interferon regulatory factor 3 protein-coding interferon regulatory factor 3 Transfection of sfRNA into JEV-infected cells also reduced phosphorylation of interferon regulatory factor-3 (IRF-3), the IFN-¦Â upstream regulator, and blocked roughly 30% of IRF-3 nuclear localization. these results suggest that sfRNA plays a role against host-cell antiviral responses, prevents cells from undergoing apoptosis, and thus contributes to viral persistence 569 SPRY4-IT1 lncRNA DGAT2 apoptosis up Homo sapiens melanoma 25344859 9606 84649 ARAT|GS1999FULL HGNC:16940|MIM:606983|Ensembl:ENSG00000062282|HPRD:07376|Vega:OTTHUMG00000165338 11 11q13.5 diacylglycerol O-acyltransferase 2 protein-coding diacylglycerol O-acyltransferase 2 SPRY4-IT1 knockdown increases the accumulation of lipin2 protein and upregulate the expression of diacylglycerol O-acyltransferase 2 (DGAT2) an enzyme involved in the conversion of DAG to triacylglycerol (TAG).Together, these results suggest the possibility that SPRY4-IT1 knockdown may induce apoptosis via lipin 2-mediated alterations in lipid metabolism leading to cellular lipotoxicity. 570 SPRY4-IT1 lncRNA EZH2 apoptosis down Homo sapiens lung cancer 24967960 9606 2146 ENX-1|ENX1|EZH1|EZH2b|KMT6|KMT6A|WVS|WVS2 HGNC:3527|MIM:601573|Ensembl:ENSG00000106462|HPRD:03342|Vega:OTTHUMG00000158973 7 7q35-q36 enhancer of zeste 2 polycomb repressive complex 2 subunit protein-coding enhancer of zeste 2 polycomb repressive complex 2 subunit SPRY4-IT1 is derived from an intron within SPRY4, and is upregulated in melanoma cells; knockdown of its expression leads to cell growth arrest, invasion inhibition, and elevated rates of apoptosis.In this study, we showed that epigenetic silencing of lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) occurs in non-small-cell lung cancer (NSCLC) cells through direct transcriptional repression mediated by the Polycomb group protein enhancer of zeste homolog 2(EZH2). 571 SPRY4-IT1 lncRNA LPIN2 apoptosis up Homo sapiens melanoma 25344859 9606 9663 - HGNC:14450|MIM:605519|Ensembl:ENSG00000101577|HPRD:16114|Vega:OTTHUMG00000131508 18 18p11.31 lipin 2 protein-coding lipin 2 SPRY4-IT1 knockdown increases the accumulation of lipin2 protein and upregulate the expression of diacylglycerol O-acyltransferase 2 (DGAT2) an enzyme involved in the conversion of DAG to triacylglycerol (TAG).Together, these results suggest the possibility that SPRY4-IT1 knockdown may induce apoptosis via lipin 2-mediated alterations in lipid metabolism leading to cellular lipotoxicity. 572 SPRY4-IT1 http://www.lncrnadb.org/Detail.aspx?TKeyID=265 lncRNA SPRY4 apoptosis down Homo sapiens melanoma cells 21558391 9606 81848 HH17 HGNC:15533|MIM:607984|Ensembl:ENSG00000187678|HPRD:10466|Vega:OTTHUMG00000129663 5 5q31.3 sprouty homolog 4 (Drosophila) protein-coding sprouty homolog 4 (Drosophila) protein sprouty homolog 4 SPRY4-IT1 RNAi knockdown results in defects in cell growth, differentiation, and higher rates of apoptosis in melanoma cell lines. We found that although the expression of both SPRY4-IT1 and SPRY4.2 varied considerably between patients samples, their relative expression levels were highly correlated (R = 0.95, Pearson correlation; Supplementary Fig. S8). 573 SPRY4-IT1 lncRNA apoptosis Homo sapiens HTR-8/SVneo 24223182 9606 The results showed that SPRY4-IT1 knockdown enhanced the cell migration and proliferation, and reduced the response of cells to apoptosis. However, exogenous SPRY4-IT1 overexpression significantly decreased the cell migration and proliferation, while increased cell apoptosis. 574 SPRY4-IT1 lncRNA apoptosis Homo sapiens prostate 25307116 9606 AK024556 (SPRY4-IT1) was highly up-regulated in human prostate cancer cell line PC3 but not in LNCaP, and siRNA knockdown of SPRY4-IT1 in PC3 cells inhibited cell proliferation and invasion and increased cell apoptosis. 575 sra http://www.lncrnadb.org/Detail.aspx?TKeyID=117 lncRNA apoptosis Homo sapiens breast cancer cells 20219889 9606 7113 PP9284|PRSS10 HGNC:11876|Ensembl:ENSG00000184012|HPRD:03637|MIM:602060|Vega:OTTHUMG00000086762 21 21q22.3 transmembrane protease, serine 2 protein coding transmembrane protease, serine 2 epitheliasin; serine prot That SRA RNA levels might affect some biological functions, such as proliferation, apoptosis, steroidogenesis, and myogenesis, has been reported. 576 T-ALL-R-lncR1 lncRNA CASP3 apoptosis down Homo sapiens T-cell acute lymphoblastic leukemia 23906015 9606 836 CPP32|CPP32B|SCA-1 HGNC:1504|MIM:600636|Ensembl:ENSG00000164305|HPRD:02799|Vega:OTTHUMG00000133681 4 4q34 caspase 3, apoptosis-related cysteine peptidase protein-coding caspase 3, apoptosis-related cysteine peptidase T-ALL-R-LncR1 knockdown predisposed Jurkat cells to undergo pro-apoptotic factor Par-4-induced apoptosis. Further studies revealed that T-ALL-R-LncR1 knockdown facilitated the formation of a Par-4/THAP1 protein complex, resulting in the activation of caspase-3 and an increase of pro-apoptotic Smac protein in T-ALL cells. 577 T-ALL-R-lncR1 lncRNA DIABLO apoptosis down Homo sapiens T-cell acute lymphoblastic leukemia 23906015 9606 56616 DFNA64|SMAC HGNC:21528|MIM:605219|Ensembl:ENSG00000184047|HPRD:05560|Vega:OTTHUMG00000157014 12 12q24.31 diablo, IAP-binding mitochondrial protein protein-coding diablo, IAP-binding mitochondrial protein T-ALL-R-LncR1 knockdown predisposed Jurkat cells to undergo pro-apoptotic factor Par-4-induced apoptosis. Further studies revealed that T-ALL-R-LncR1 knockdown facilitated the formation of a Par-4/THAP1 protein complex, resulting in the activation of caspase-3 and an increase of pro-apoptotic Smac protein in T-ALL cells. 578 T-ALL-R-lncR1 lncRNA PAWR apoptosis down Homo sapiens T-cell acute lymphoblastic leukemia 23906015 9606 5074 PAR4|Par-4 HGNC:8614|MIM:601936|HPRD:09051 12 12q21 PRKC, apoptosis, WT1, regulator protein-coding PRKC, apoptosis, WT1, regulator T-ALL-R-LncR1 knockdown predisposed Jurkat cells to undergo pro-apoptotic factor Par-4-induced apoptosis. Further studies revealed that T-ALL-R-LncR1 knockdown facilitated the formation of a Par-4/THAP1 protein complex, resulting in the activation of caspase-3 and an increase of pro-apoptotic Smac protein in T-ALL cells. 579 T-ALL-R-lncR1 lncRNA THAP1 apoptosis down Homo sapiens T-cell acute lymphoblastic leukemia 23906015 9606 55145 DYT6 HGNC:20856|MIM:609520|Ensembl:ENSG00000131931|HPRD:15496|Vega:OTTHUMG00000165276 8 8p11.21 THAP domain containing, apoptosis associated protein 1 protein-coding THAP domain containing, apoptosis associated protein 1 T-ALL-R-LncR1 knockdown predisposed Jurkat cells to undergo pro-apoptotic factor Par-4-induced apoptosis. Further studies revealed that T-ALL-R-LncR1 knockdown facilitated the formation of a Par-4/THAP1 protein complex, resulting in the activation of caspase-3 and an increase of pro-apoptotic Smac protein in T-ALL cells. 580 TINCR lncRNA CDKN1A apoptosis Homo sapiens gastric carcinoma 25728677 9606 1026 CAP20|CDKN1|CIP1|MDA-6|P21|SDI1|WAF1|p21CIP1 HGNC:1784|MIM:116899|Ensembl:ENSG00000124762|HPRD:00298|Vega:OTTHUMG00000014603 6 6p21.2 cyclin-dependent kinase inhibitor 1A (p21, Cip1) protein-coding cyclin-dependent kinase inhibitor 1A (p21, Cip1) Mechanistic analyses indicated that TINCR could bind to STAU1 (staufen1) protein, and influence KLF2 mRNA stability and expression, then KLF2 regulated cyclin-dependent kinase genes CDKN1A/P21 and CDKN2B/P15 transcription and expression, thereby affecting the proliferation and?apoptosis?of GC cells. 581 TINCR lncRNA CDKN2B apoptosis Homo sapiens gastric carcinoma 25728677 9606 1030 CDK4I|INK4B|MTS2|P15|TP15|p15INK4b HGNC:1788|MIM:600431|Ensembl:ENSG00000147883|HPRD:02696|Vega:OTTHUMG00000019691 9 9p21 cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) protein-coding cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) Mechanistic analyses indicated that TINCR could bind to STAU1 (staufen1) protein, and influence KLF2 mRNA stability and expression, then KLF2 regulated cyclin-dependent kinase genes CDKN1A/P21 and CDKN2B/P15 transcription and expression, thereby affecting the proliferation and?apoptosis?of GC cells. 582 TINCR lncRNA KLF2 apoptosis Homo sapiens gastric carcinoma 25728677 9606 10365 LKLF HGNC:6347|MIM:602016|Ensembl:ENSG00000127528|HPRD:03602|Vega:OTTHUMG00000182330 19 19p13.11 Kruppel-like factor 2 protein-coding Kruppel-like factor 2 Mechanistic analyses indicated that TINCR could bind to STAU1 (staufen1) protein, and influence KLF2 mRNA stability and expression, then KLF2 regulated cyclin-dependent kinase genes CDKN1A/P21 and CDKN2B/P15 transcription and expression, thereby affecting the proliferation and?apoptosis?of GC cells. 583 TINCR lncRNA SP1 apoptosis Homo sapiens gastric carcinoma 25728677 9606 6667 - HGNC:11205|MIM:189906|Ensembl:ENSG00000185591|HPRD:01796|Vega:OTTHUMG00000170047 12 12q13.1 Sp1 transcription factor protein-coding Sp1 transcription factor We also revealed that TINCR overexpression is induced by nuclear transcription factor SP1. Silencing TINCR expression inhibited cell proliferation, colony formation, tumorigenicity and?apoptosis?promotion, whereas TINCR overexpression promoted cell growth, as documented in the SGC7901 and BGC823 cell lines. 584 TINCR lncRNA STAU1 apoptosis Homo sapiens gastric carcinoma 25728677 9606 6780 PPP1R150|STAU HGNC:11370|MIM:601716|Ensembl:ENSG00000124214|HPRD:03422|Vega:OTTHUMG00000032691 20 20q13.1 staufen double-stranded RNA binding protein 1 protein-coding staufen double-stranded RNA binding protein 1 Mechanistic analyses indicated that TINCR could bind to STAU1 (staufen1) protein, and influence KLF2 mRNA stability and expression, then KLF2 regulated cyclin-dependent kinase genes CDKN1A/P21 and CDKN2B/P15 transcription and expression, thereby affecting the proliferation and?apoptosis?of GC cells. 585 TUG1 http://www.lncrnadb.org/Detail.aspx?TKeyID=120 lncRNA apoptosis up Homo sapiens HeLa and caspase-3-deficient MCF-7 cell 22487937 9606 Our results reveal that basal RNA expression levels as well as the changes in the lncRNA expression rates during genotoxic stress-induced apoptosis were cell-type and/or DNA-damaging agent-specific. Generally, we found that some of the RNA molecules (HOTAIR and MALAT1) are down-regulated while many of them (lincRNA-p21, GAS5, MEG3, ANRIL, and ncRNA-CCND1) are up-regulated and some others (TUG1, UCA1, and PANDA) not affected. 586 TUG1 http://www.lncrnadb.org/Detail.aspx?TKeyID=120 lncRNA apoptosis Homo sapiens bladder urothelial carcinoma cells 22961206 9606 Cell proliferation inhibition and apoptosis induction were observed in TUG1 siRNA-transfected bladder urothelial carcinoma T24 and 5637 cells. 587 TUG1 lncRNA apoptosis Homo sapiens osteosarcoma 23725133 9606 Furthermore, inhibition of TUG1 expression significantly promoted osteosarcoma cell apoptosis. 588 uc.73A lncRNA apoptosis Homo sapiens colon cancer cells 22664915 9606 Depletion of uc.73A ncRNA resulted in reduced cellular proliferation of COLO-320 cells and an increase in sub-G1 cells, suggesting higher apoptosis rates. Thus, uc.73A(P) could act as an oncogene by increasing the number of malignant cells as a consequence of reduced apoptosis. 589 uc002mbe.2 http://www.ncbi.nlm.nih.gov/gene/?term=uc002mbe.2++human lncRNA apoptosis Homo sapiens Hepatocellular carcinoma Huh7 23643933 9606 8743 PRP|TSA|PRX2|PTX1|TPX1|NKEFB|PRXII|TDPX1|NKEF-B|HEL-S-2a HGNC:9353|Ensembl:ENSG00000167815|HPRD:02763|MIM:600538|Vega:OTTHUMG00000134285 19 19p13.2 peroxiredoxin 2 protein coding peroxiredoxin 2 Knockdown the expression of uc002mbe.2 significantly reduced TSA-induced apoptosis of Huh7cells. 590 UCA1 lncRNA CEBPA apoptosis down Homo sapiens bladder 24648007 9606 1050 C/EBP-alpha|CEBP HGNC:1833|MIM:116897|Ensembl:ENSG00000245848|HPRD:00296|Vega:OTTHUMG00000161461 19 19q13.1 CCAAT/enhancer binding protein (C/EBP), alpha protein-coding CCAAT/enhancer binding protein (C/EBP), alpha Upregulation of long non-coding RNA urothelial carcinoma associated 1 by CCAAT/enhancer binding protein ¦Á contributes to bladder cancer cell growth and reduced apoptosis.Electrophoretic mobility shift assay and chromatin immunoprecipitation assay indicated that C/EBP¦Á bound to the lncRNA-UCA1 core promoter region in vitro and in vivo. 591 UCA1 lncRNA HIF1A apoptosis down Homo sapiens bladder 24737584 9606 3091 HIF-1A|HIF-1alpha|HIF1|HIF1-ALPHA|MOP1|PASD8|bHLHe78 HGNC:4910|MIM:603348|Ensembl:ENSG00000100644|HPRD:04517|Vega:OTTHUMG00000140344 14 14q23.2 hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) protein-coding hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) lncRNA-UCA1 upregulation increased cell proliferation, migration, and invasion and inhibited apoptosis.The underlying mechanism of hypoxia-upregulated lncRNA-UCA1 expression was that HIF-1¦Á specifically bound to HREs in the lncRNA-UCA1 promoter. 592 UCA1 http://www.ncbi.nlm.nih.gov/gene/652995 lncRNA apoptosis up Homo sapiens HeLa and caspase-3-deficient MCF-7 cell 22487937 9606 Our results reveal that basal RNA expression levels as well as the changes in the lncRNA expression rates during genotoxic stress-induced apoptosis were cell-type and/or DNA-damaging agent-specific. Generally, we found that some of the RNA molecules (HOTAIR and MALAT1) are down-regulated while many of them (lincRNA-p21, GAS5, MEG3, ANRIL, and ncRNA-CCND1) are up-regulated and some others (TUG1, UCA1, and PANDA) not affected. 593 UCA1 http://www.lncrnadb.org/Detail.aspx?TKeyID=121 lncRNA apoptosis Homo sapiens bladder cancer cells 22576688 9606 Overexpression of UCA1a(CUDR) could antagonize cell apoptosis induced by cisplatin and promote the tumorigenicity of UM-UC-2 cells in vivo. 594 UCA1 lncRNA apoptosis Homo sapiens colorectal cancer 24977734 9606 UCA1 was found to influence the proliferation, apoptosis and cell cycle progression of CRC cells. 595 URH lncRNA ZAK apoptosis down Homo sapiens hepatocellular carcinoma 25013376 9606 51776 AZK|MLK7|MLT|MLTK|MRK|mlklak|pk MIM:609479|Ensembl:ENSG00000091436|HPRD:11791|Vega:OTTHUMG00000132297 2 2q24.2 sterile alpha motif and leucine zipper containing kinase AZK protein-coding - We concluded that high URHC expression can promote cell proliferation and inhibit apoptosis by repressing ZAK expression through inactivation of the ERK/MAPK pathway. 596 Xist http://www.lncrnadb.org/Detail.aspx?TKeyID=122 lncRNA DNMT1 apoptosis Homo sapiens embryonic stem cells 8769643 9606 1786 ADCADN|AIM|CXXC9|DNMT|HSN1E|MCMT HGNC:2976|MIM:126375|Ensembl:ENSG00000130816|HPRD:00532|Vega:OTTHUMG00000180397 19 19p13.2 DNA (cytosine-5-)-methyltransferase 1 protein-coding DNA (cytosine-5-)-methyltransferase 1 In differentiated Dnmt mutant ES cells the activation of Xist expression correlated with a dramatic increase in apoptotic bodies, suggesting that Xist-mediated X chromosome inactivation may result in cell death and contribute to the embryonic lethality of the Dnmt mutation. 597 Xist lncRNA POU5F1 apoptosis down Homo sapiens 24945968 9606 5460 OCT3|OCT4|OTF-3|OTF3|OTF4|Oct-3|Oct-4 HGNC:9221|MIM:164177|Ensembl:ENSG00000204531|HPRD:01252|Vega:OTTHUMG00000031206 6 6p21.31 POU class 5 homeobox 1 protein-coding POU class 5 homeobox 1 We observed higher rates of blastocyst formation (P? 0.05). 1283 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA GAS5 apoptosis down Homo sapiens 23933812 9606 60674 NCRNA00030|SNHG2 HGNC:16355|MIM:608280|Ensembl:ENSG00000234741 1 1q25.1 growth arrest-specific 5 (non-protein coding) ncRNA growth arrest-specific 5 (non-protein coding) Using the lncRNA RT-PCR (reverse transcription-polymerase chain reaction) array carrying 83 human disease-related lncRNAs, we show that miR-21 is capable of suppressing the lncRNA growth arrest-specific 5 (GAS5). Of interest, GAS5 can also repress miR-21 expression. 1284 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA GAS5 apoptosis Homo sapiens osteoarthritis 25196583 9606 60674 NCRNA00030|SNHG2 HGNC:16355|MIM:608280|Ensembl:ENSG00000234741 1 1q25.1 growth arrest-specific 5 (non-protein coding) ncRNA growth arrest-specific 5 (non-protein coding) Together,these results show that GAS5 contributes to the pathogenesis of OA by acting as a negative regulator of miR-21 and thereby regulating cell survival. 1285 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA MKI67 apoptosis down Homo sapiens tongue squamous cell 21426775 9606 4288 KIA|MIB-|MIB-1|PPP1R105 HGNC:7107|MIM:176741|Ensembl:ENSG00000148773|HPRD:08902|Vega:OTTHUMG00000019255 10 10q26.2 marker of proliferation Ki-67 protein-coding marker of proliferation Ki-67 MiRNA-21 expression was decreased in miRNA-21 antisense oligonucleotide (ASODN) group. The survival rate of Tb 3.1 cells with AS-miRNA-21 transfection was significantly suppressed (F = 27.02, P = 0.00) and early phase apoptosis (F = 26.641, P = 0.001) induced in Tb 3.1 cell. Ki67, Bcl-2, MMP-2 and MMP-9 protein were down regulated while PTEN and TIMP-1 protein expression was increased. 1286 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA MMP2 apoptosis down Homo sapiens tongue squamous cell 21426775 9606 4313 CLG4|CLG4A|MMP-II|MONA|TBE-1 HGNC:7166|MIM:120360|Ensembl:ENSG00000087245|HPRD:00386|Vega:OTTHUMG00000133202 16 16q13-q21 matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase) protein-coding matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase) MiRNA-21 expression was decreased in miRNA-21 antisense oligonucleotide (ASODN) group. The survival rate of Tb 3.1 cells with AS-miRNA-21 transfection was significantly suppressed (F = 27.02, P = 0.00) and early phase apoptosis (F = 26.641, P = 0.001) induced in Tb 3.1 cell. Ki67, Bcl-2, MMP-2 and MMP-9 protein were down regulated while PTEN and TIMP-1 protein expression was increased. 1287 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA MMP9 apoptosis down Homo sapiens tongue squamous cell 21426775 9606 4318 CLG4B|GELB|MANDP2|MMP-9 HGNC:7176|MIM:120361|Ensembl:ENSG00000100985|HPRD:00387|Vega:OTTHUMG00000033044 20 20q11.2-q13.1 matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) protein-coding matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) MiRNA-21 expression was decreased in miRNA-21 antisense oligonucleotide (ASODN) group. The survival rate of Tb 3.1 cells with AS-miRNA-21 transfection was significantly suppressed (F = 27.02, P = 0.00) and early phase apoptosis (F = 26.641, P = 0.001) induced in Tb 3.1 cell. Ki67, Bcl-2, MMP-2 and MMP-9 protein were down regulated while PTEN and TIMP-1 protein expression was increased. 1288 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA NFKB1 apoptosis Homo sapiens 25000291 9606 4790 EBP-1|KBF1|NF-kB1|NF-kappa-B|NF-kappaB|NFKB-p105|NFKB-p50|NFkappaB|p105|p50 HGNC:7794|MIM:164011|Ensembl:ENSG00000109320|HPRD:01238|Vega:OTTHUMG00000161080 4 4q24 nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 protein-coding nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 MPT64 protein from Mycobacterium tuberculosis inhibits apoptosis of macrophages through NF-kB-miRNA21-Bcl-2 pathway.Furthermore, the results provided strong evidence that bcl-2 up-regulation was positively controlled by miRNA-21. Finally, NF-¦ÊB was identified as the transcription factor for miRNA-21 using a ChIP assay. It can be concluded from our study that MPT64 could inhibit the apoptosis of RAW264.7 macrophages through the NF-¦ÊB-miRNA21-Bcl-2 pathway. 1289 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PDCD4 apoptosis Homo sapiens breast cancer cells 17991735 9606 27250 H731 HGNC:8763|MIM:608610|Ensembl:ENSG00000150593|HPRD:10549|Vega:OTTHUMG00000019048 10 10q24 programmed cell death 4 (neoplastic transformation inhibitor) protein-coding programmed cell death 4 (neoplastic transformation inhibitor) neoplastic transformation The miR-21 microRNA is overexpressed in a wide variety of cancers and has been causally linked to cellular proliferation, apoptosis, and migration. Inhibition of mir-21 in MCF-7 breast cancer cells causes reduced cell growth. Using array expression analysis of MCF-7 cells depleted of miR-21, we have identified mRNA targets of mir-21 and have shown a link between miR-21 and the p53 tumor suppressor protein. We furthermore found that the tumor suppressor protein Programmed Cell Death 4 (PDCD4) is regulated by miR-21 and demonstrated that PDCD4 is a functionally important target for miR-21 in breast cancer cells. 1290 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PDCD4 apoptosis Homo sapiens cardiac myocytes 19336275 9606 27250 H731 HGNC:8763|MIM:608610|Ensembl:ENSG00000150593|HPRD:10549|Vega:OTTHUMG00000019048 10 10q24 programmed cell death 4 (neoplastic transformation inhibitor) protein-coding programmed cell death 4 (neoplastic transformation inhibitor) To determine the potential roles of miRNAs in H(2)O(2)-mediated gene regulation and cellular injury, miR-21 expression was downregulated by miR-21 inhibitor and upregulated by pre-miR-21. H(2)O(2)-induced cardiac cell death and apoptosis were increased by miR-21 inhibitor and was decreased by pre-miR-21. Programmed cell death 4 (PDCD4) that was regulated by miR-21 and was a direct target of miR-21 in cardiac myocytes. 1291 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PDCD4 apoptosis up Homo sapiens K562 cells 20141427 9606 27250 H731 HGNC:8763|MIM:608610|Ensembl:ENSG00000150593|HPRD:10549|Vega:OTTHUMG00000019048 10 10q24 programmed cell death 4 (neoplastic transformation inhibitor) protein-coding programmed cell death 4 (neoplastic transformation inhibitor) In this study, we found that the antisense inhibition of miR-21 in K562 cells suppressed cell migration, promoted cell apoptosis, and inhibited cell growth, and up-regulated the expression of the tumor suppressor gene PDCD4. Meanwhile, pre-miRNA-21 increased migration and decreased cell apoptosis without affecting proliferation. 1292 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PDCD4 apoptosis Homo sapiens chronic myeloid leukemia cells 20148895 9606 27250 H731 HGNC:8763|MIM:608610|Ensembl:ENSG00000150593|HPRD:10549|Vega:OTTHUMG00000019048 10 10q24 programmed cell death 4 (neoplastic transformation inhibitor) protein-coding programmed cell death 4 (neoplastic transformation inhibitor) neoplastic transformation AMO-miR-21 sensitized leukemic K562 cells to ATO by inducing apoptosis partially due to its up-regulation of PDCD4 protein level. 1293 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PDCD4 apoptosis down Homo sapiens HCC cell 20447717 9606 27250 H731 HGNC:8763|MIM:608610|Ensembl:ENSG00000150593|HPRD:10549|Vega:OTTHUMG00000019048 10 10q24 programmed cell death 4 (neoplastic transformation inhibitor) protein-coding programmed cell death 4 (neoplastic transformation inhibitor) We demonstrate that hepatocellular carcinoma is characterized by elevated levels of microRNA-21 and marked reductions of PTEN, PDCD4, and RECK expression. Silencing of PTEN and PDCD4 to prevent their induction by anti-microRNA-21 treatment led to decreased apoptosis and increased invasion, while silencing of RECK only led to increased invasion. 1294 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PDCD4 apoptosis Homo sapiens Cardiovascular cell 20560046 9606 27250 H731 HGNC:8763|MIM:608610|Ensembl:ENSG00000150593|HPRD:10549|Vega:OTTHUMG00000019048 10 10q24 programmed cell death 4 (neoplastic transformation inhibitor) protein-coding programmed cell death 4 (neoplastic transformation inhibitor) MiR-21 is found to play important roles in vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. Programmed cell death 4 (PDCD4), phosphatase and tensin homology deleted from chromosome 10 (PTEN), sprouty1 (SPRY1), and sprouty2 (SPRY2) are the current identified target genes of miR-21 that are involved in miR-21-mediated cardiovascular effects. 1295 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PDCD4 apoptosis down Homo sapiens promyelocytic leukemia cells 20670480 9606 27250 H731 HGNC:8763|MIM:608610|Ensembl:ENSG00000150593|HPRD:10549|Vega:OTTHUMG00000019048 10 10q24 programmed cell death 4 (neoplastic transformation inhibitor) protein-coding programmed cell death 4 (neoplastic transformation inhibitor) neoplastic transformation Anti-miR-21 oligonucleotide enhances chemosensitivity of leukemic HL60 cells to arabinosylcytosine by inducing apoptosis. 1296 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PDCD4 apoptosis up Homo sapiens glioblastoma-derived cells 21636706 9606 27250 H731 HGNC:8763|MIM:608610|Ensembl:ENSG00000150593|HPRD:10549|Vega:OTTHUMG00000019048 10 10q24 programmed cell death 4 (neoplastic transformation inhibitor) protein-coding programmed cell death 4 (neoplastic transformation inhibitor) neoplastic transformation Either downregulation of mir-21 or overexpression of its target, Pdcd4, in glioblastoma-derived cell lines leads to decreased proliferation, increased apoptosis, and decreased colony formation in soft agar. 1297 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PDCD4 apoptosis down Homo sapiens 21763111 9606 27250 H731 HGNC:8763|MIM:608610|Ensembl:ENSG00000150593|HPRD:10549|Vega:OTTHUMG00000019048 10 10q24 programmed cell death 4 (neoplastic transformation inhibitor) protein-coding programmed cell death 4 (neoplastic transformation inhibitor) The respective targets of miRNA-21 and -106a, the tumor suppressors PTEN, PDCD4 and Rb with their pivotal role in cell cycle regulation, apoptosis and proliferation were found to be downregulated. 1298 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PDCD4 apoptosis down Homo sapiens human glioblastoma cell lines cells 22353043 9606 27250 H731 HGNC:8763|MIM:608610|Ensembl:ENSG00000150593|HPRD:10549|Vega:OTTHUMG00000019048 10 10q24 programmed cell death 4 (neoplastic transformation inhibitor) protein-coding programmed cell death 4 (neoplastic transformation inhibitor) And over-expression of miR-21 in U251 cells abolished the enhancement of PDCD4 protein by UA. 1299 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PDCD4 apoptosis down Homo sapiens malignant peripheral nerve sheath tumor cells 22526161 9606 27250 H731 HGNC:8763|MIM:608610|Ensembl:ENSG00000150593|HPRD:10549|Vega:OTTHUMG00000019048 10 10q24 programmed cell death 4 (neoplastic transformation inhibitor) protein-coding programmed cell death 4 (neoplastic transformation inhibitor) In MPNST cells, transfection of miR-21 inhibitor significantly increased caspase activity (P < 0.01), significantly suppressed cell growth (P < 0.05), and upregulated protein level of PDCD4, indicating that miR-21 inhibitor could induce cell apoptosis of MPNST cells. 1300 miR-21 hsa-miR-21-5p,hsa-miR-211-5p,hsa-miR-212-3p,hsa-miR-214-3p,hsa-miR-216 MIMAT0000076,MIMAT0000268,MIMAT0000269,MIMAT000027 miRNA PDCD4 apoptosis down Homo sapiens breast cancer cells 22547075 9606 27250 H731 HGNC:8763|MIM:608610|Ensembl:ENSG00000150593|HPRD:10549|Vega:OTTHUMG00000019048 10 10q24 programmed cell death 4 (neoplastic transformation inhibitor) protein-coding programmed cell death 4 (neoplastic transformation inhibitor) Induction of miR-21 may enable cancer cells to elude DNA damage-induced apoptosis and enhance the metastatic potential of breast cancer cells through repressing expression of PTEN and PDCD4. 1301 miR-21 hsa-miR-21-5p,hsa-miR-211-5p,hsa-miR-212-3p,hsa-miR-214-3p,hsa-miR-216 MIMAT0000076,MIMAT0000268,MIMAT0000269,MIMAT000027 miRNA PDCD4 apoptosis down Homo sapiens adventitial fibroblasts and myofibroblasts cells 22565856 9606 27250 H731 HGNC:8763|MIM:608610|Ensembl:ENSG00000150593|HPRD:10549|Vega:OTTHUMG00000019048 10 10q24 programmed cell death 4 (neoplastic transformation inhibitor) protein-coding programmed cell death 4 (neoplastic transformation inhibitor) Programmed cell death 4 (PDCD4), related to cell proliferation and apoptosis, was validated as a direct target of miR-21 by dual-luciferase reporter assay and gain and loss of function of miR-21 in AFs and MFs. PDCD4 knockdown with siRNA partly rescued the reduced proliferation with miR-21 inhibition and alleviated the increased apoptosis induced by miR-21 inhibition in AFs and MFs. 1302 miR-21 hsa-miR-21-5p,hsa-miR-211-5p,hsa-miR-212-3p,hsa-miR-214-3p,hsa-miR-216 MIMAT0000076,MIMAT0000268,MIMAT0000269,MIMAT000027 miRNA PDCD4 apoptosis down Homo sapiens cultured immortalized myometrial and leiomyoma cells 22728051 9606 27250 H731 HGNC:8763|MIM:608610|Ensembl:ENSG00000150593|HPRD:10549|Vega:OTTHUMG00000019048 10 10q24 programmed cell death 4 (neoplastic transformation inhibitor) protein-coding programmed cell death 4 (neoplastic transformation inhibitor) Loss of miR-21 also increased cleavage of caspase-3 (apoptosis marker) and increased phosphorylation of elongation factor-2 (marker of reduced translation) in both cell lines. Our studies indicate regulation of PDCD-4 expression is not a primary miR-21 function in leiomyomas, but instead miR-21 is able to impact cellular apoptosis and translation, through unknown targets, in a manner consistent with its involvement in the pathophysiology of uterine fibroids. 1303 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PDCD4 apoptosis down Homo sapiens myocardial 23544605 9606 27250 H731 HGNC:8763|MIM:608610|Ensembl:ENSG00000150593|HPRD:10549|Vega:OTTHUMG00000019048 10 10q24 programmed cell death 4 (neoplastic transformation inhibitor) protein-coding programmed cell death 4 (neoplastic transformation inhibitor) Further study showed that miR-21 could protect myocardial apoptosis by specifically inhibiting its target programmed cell death 4 (PDCD4) expression. 1304 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PDCD4 apoptosis down Homo sapiens renal cell carcinoma cells 23558936 9606 27250 H731 HGNC:8763|MIM:608610|Ensembl:ENSG00000150593|HPRD:10549|Vega:OTTHUMG00000019048 10 10q24 programmed cell death 4 (neoplastic transformation inhibitor) protein-coding programmed cell death 4 (neoplastic transformation inhibitor) Furthermore, miR-21 mimic or inhibitor significantly reduced or increased the expression of PDCD4 and TPM1. 1305 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PDCD4 apoptosis down Homo sapiens ovarian 24472409 9606 27250 H731 HGNC:8763|MIM:608610|Ensembl:ENSG00000150593|HPRD:10549|Vega:OTTHUMG00000019048 10 10q24 programmed cell death 4 (neoplastic transformation inhibitor) protein-coding programmed cell death 4 (neoplastic transformation inhibitor) Using Western blot analysis, miR-21 knockdown enhanced the expression of tumor suppressor PDCD4, and attenuated apoptosis inhibitor c-IAP2. 1306 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PDCD4 apoptosis down Homo sapiens Papillary thyroid carcinoma cell 24650454 9606 27250 H731 HGNC:8763|MIM:608610|Ensembl:ENSG00000150593|HPRD:10549|Vega:OTTHUMG00000019048 10 10q24 programmed cell death 4 (neoplastic transformation inhibitor) protein-coding programmed cell death 4 (neoplastic transformation inhibitor) Overexpression of miRNA-21 could significantly enhance proliferation and invasion and inhibit the apoptosis of TPC-1 cells. In addition, miRNA-21 and PDCD4 expression showed a significantly negative correlation in TPC-1 cells. 1307 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PTEN apoptosis down Homo sapiens cholangiocarcinoma cell 16762633 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog MiR-21 modulates gemcitabine-induced apoptosis by phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-dependent activation of PI 3-kinase signaling. Potential target genes that were modulated by selected miRNA were identified. 1308 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PTEN apoptosis down Homo sapiens cholesteatoma cells 19672202 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog Up-regulation of hsa-miR-21 concurrent with down-regulation of potent tumor suppressor proteins PTEN and programmed cell death 4. these proteins control aspects of apoptosis, proliferation, invasion, and migration. 1309 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PTEN apoptosis down Homo sapiens U251 20048743 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog To explore whether miR-21 can serve as a therapeutic target for glioblastoma, we downregulated miR-21 with a specific antisense oligonucleotide and found that apoptosis was induced and cell-cycle progression was inhibited in vitro in U251 (PTEN mutant) and LN229 (PTEN wild-type) GBM cells; xenograft tumors from antisense-treated U251 cells were suppressed in vivo. 1310 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PTEN apoptosis down Homo sapiens endothelial cell 20153722 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog Western analysis demonstrated that PTEN, a known target of miR-21, was downregulated in HUVECs exposed to USS or transfected with pre-miR-21. Importantly, HUVECs overexpressing miR-21 had decreased apoptosis and increased eNOS phosphorylation and nitric oxide (NO(*)) production. These data demonstrate that shear stress forces regulate the expression of miRNAs in ECs, and that miR-21 influences endothelial biology by decreasing apoptosis and activating the NO(*) pathway. These studies advance our understanding of the mechanisms by which shear stress forces modulate vascular homeostasis. 1311 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PTEN apoptosis down Homo sapiens HCC cell 20447717 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog We demonstrate that hepatocellular carcinoma is characterized by elevated levels of microRNA-21 and marked reductions of PTEN, PDCD4, and RECK expression. Silencing of PTEN and PDCD4 to prevent their induction by anti-microRNA-21 treatment led to decreased apoptosis and increased invasion, while silencing of RECK only led to increased invasion. 1312 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PTEN apoptosis Homo sapiens Cardiovascular cell 20560046 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog MiR-21 is found to play important roles in vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. Programmed cell death 4 (PDCD4), phosphatase and tensin homology deleted from chromosome 10 (PTEN), sprouty1 (SPRY1), and sprouty2 (SPRY2) are the current identified target genes of miR-21 that are involved in miR-21-mediated cardiovascular effects. 1313 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PTEN apoptosis up Homo sapiens tongue squamous cell 21426775 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog MiRNA-21 expression was decreased in miRNA-21 antisense oligonucleotide (ASODN) group. The survival rate of Tb 3.1 cells with AS-miRNA-21 transfection was significantly suppressed (F = 27.02, P = 0.00) and early phase apoptosis (F = 26.641, P = 0.001) induced in Tb 3.1 cell. Ki67, Bcl-2, MMP-2 and MMP-9 protein were down regulated while PTEN and TIMP-1 protein expression was increased. 1314 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PTEN apoptosis down Homo sapiens 21763111 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog The respective targets of miRNA-21 and -106a, the tumor suppressors PTEN, PDCD4 and Rb with their pivotal role in cell cycle regulation, apoptosis and proliferation were found to be downregulated. 1315 miR-21 hsa-miR-21-5p,hsa-miR-211-5p,hsa-miR-212-3p,hsa-miR-214-3p,hsa-miR-216 MIMAT0000076,MIMAT0000268,MIMAT0000269,MIMAT000027 miRNA PTEN apoptosis down Homo sapiens breast cancer cells 22547075 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog Induction of miR-21 may enable cancer cells to elude DNA damage-induced apoptosis and enhance the metastatic potential of breast cancer cells through repressing expression of PTEN and PDCD4. 1316 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA PTEN apoptosis down Homo sapiens cardiomyocytes 23710745 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog MicroRNA-21 reduced TNF-¦Á induced cardiomyocytes apoptosis [(23.42 ¡À 1.98)% vs. (78.37 ¡À 2.03)%, P < 0.05]. TNF-¦Á downregulated the expression of microRNA-21 and upregulated the mRNA and protein expressions of PTEN. Phosphorylation of PTEN, AKT and FOXO3a was enhanced in cardiomyocytes transfected with lenti-microRNA-21 (P < 0.05). TNF-¦Á also significantly activated the phosphorylation of PTEN, AKT and FOXO3a (P < 0.05). Compared with cardiomyocytes treated with TNF-¦Á (10 ng/ml), the phosphorylation of PTEN, AKT and FOXO3a as well as expression of pPTEN, pAKTser473, pFOXO3a and FasL were significantly suppressed in cardiomyocytes treated with lenti-microRNA-21 and TNF-¦Á (P < 0.05). Total AKT and FOXO3a were similar among all groups (P > 0.05). 1317 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA RB1 apoptosis down Homo sapiens 21763111 9606 5925 OSRC|PPP1R130|RB|p105-Rb|pRb|pp110 HGNC:9884|MIM:614041|Ensembl:ENSG00000139687|HPRD:01574|Vega:OTTHUMG00000016900 13 13q14.2 retinoblastoma 1 protein-coding retinoblastoma 1 The respective targets of miRNA-21 and -106a, the tumor suppressors PTEN, PDCD4 and Rb with their pivotal role in cell cycle regulation, apoptosis and proliferation were found to be downregulated. 1318 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA RECK apoptosis up Homo sapiens gastric cancer cells 18794849 9606 8434 ST15 HGNC:11345|MIM:605227|Ensembl:ENSG00000122707|HPRD:05567|Vega:OTTHUMG00000019898 9 9p13.3 reversion-inducing-cysteine-rich protein with kazal motifs protein-coding reversion-inducing-cysteine-rich protein with kazal motifs membrane-anchored glycopr More importantly, we showed that forced expression of miR-21 significantly enhanced cell proliferation and invasion in AGS cells, a human gastric cancer cell line, whereas knockdown of miR-21 by inhibitor caused a significant reduction in cell proliferation and a significant increase in apoptosis. Furthermore, we demonstrated that knockdown of miR-21 significantly decreased cell invasion and migration of AGS cells. Finally, we showed that RECK, a known tumor suppressor in gastric cancer, is a bona fide target of miR-21.? 1319 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA RECK apoptosis down Homo sapiens esophageal carcinoma 23504349 9606 8434 ST15 HGNC:11345|MIM:605227|Ensembl:ENSG00000122707|HPRD:05567|Vega:OTTHUMG00000019898 9 9p13.3 reversion-inducing-cysteine-rich protein with kazal motifs protein-coding reversion-inducing-cysteine-rich protein with kazal motifs miR-21 expression was increased significantly in ESCC tissues compared with NMAT. miR-21 down-regulation inhibits cell growth, cell invasion and induces cells to apoptosis. FASL, TIMP3 and RECK are direct targets of miR-21. 1320 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA SETD7 apoptosis up Homo sapiens human multiple myeloma cells 23247593 9606 80854 KMT7|SET7|SET7/9|SET9 HGNC:30412|MIM:606594|Ensembl:ENSG00000145391|HPRD:16226|Vega:OTTHUMG00000133385 4 4q28 SET domain containing (lysine methyltransferase) 7 protein-coding SET domain containing (lysine methyltransferase) 7 In U266 cells, berberine suppresses NF-¦ÊB nuclear translocation via Set9-mediated lysine methylation, leads to decrease in the levels miR21 and Bcl-2, which induces ROS generation and apoptosis. 1321 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA SPRY1 apoptosis Homo sapiens Cardiovascular cell 20560046 9606 10252 hSPRY1 HGNC:11269|MIM:602465|Ensembl:ENSG00000164056|HPRD:06782|Vega:OTTHUMG00000133071 4 4q28.1 sprouty homolog 1, antagonist of FGF signaling (Drosophila) protein-coding sprouty homolog 1, antagonist of FGF signaling (Drosophila) MiR-21 is found to play important roles in vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. Programmed cell death 4 (PDCD4), phosphatase and tensin homology deleted from chromosome 10 (PTEN), sprouty1 (SPRY1), and sprouty2 (SPRY2) are the current identified target genes of miR-21 that are involved in miR-21-mediated cardiovascular effects. 1322 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA SPRY2 apoptosis Homo sapiens Cardiovascular cell 20560046 9606 10253 hSPRY2 HGNC:11270|MIM:602466|Ensembl:ENSG00000136158|HPRD:03916|Vega:OTTHUMG00000017140 13 13q31.1 sprouty homolog 2 (Drosophila) protein-coding sprouty homolog 2 (Drosophila) MiR-21 is found to play important roles in vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. Programmed cell death 4 (PDCD4), phosphatase and tensin homology deleted from chromosome 10 (PTEN), sprouty1 (SPRY1), and sprouty2 (SPRY2) are the current identified target genes of miR-21 that are involved in miR-21-mediated cardiovascular effects. 1323 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA STAT3 apoptosis up Homo sapiens CD4+ tumor cell 21085192 9606 6774 APRF|HIES HGNC:11364|MIM:102582|Ensembl:ENSG00000168610|HPRD:00026|Vega:OTTHUMG00000150645 17 17q21.31 signal transducer and activator of transcription 3 (acute-phase response factor) protein-coding signal transducer and activator of transcription 3 (acute-phase response factor) Stimulation of S¨¦zary cells or healthy CD4+ T cells with the common-¦Ã chain cytokine IL-21 results in a strong activation of STAT3, and subsequent upregulation of miR-21 expression. Both pri- and mature miR-21 expression are increased in S¨¦zary cells when compared with CD4+ T cells from healthy donors. Silencing of miR-21 in S¨¦zary cells results in increased apoptosis, suggesting a functional role for miR-21 in the leukomogenic process. Consequently, miR-21 might represent a therapeutic target for the treatment of SS. 1324 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA TIMP1 apoptosis up Homo sapiens tongue squamous cell 21426775 9606 7076 CLGI|EPA|EPO|HCI|TIMP HGNC:11820|MIM:305370|Ensembl:ENSG00000102265|HPRD:02371|Vega:OTTHUMG00000021447 X Xp11.3-p11.23 TIMP metallopeptidase inhibitor 1 protein-coding TIMP metallopeptidase inhibitor 1 MiRNA-21 expression was decreased in miRNA-21 antisense oligonucleotide (ASODN) group. The survival rate of Tb 3.1 cells with AS-miRNA-21 transfection was significantly suppressed (F = 27.02, P = 0.00) and early phase apoptosis (F = 26.641, P = 0.001) induced in Tb 3.1 cell. Ki67, Bcl-2, MMP-2 and MMP-9 protein were down regulated while PTEN and TIMP-1 protein expression was increased. 1325 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA TIMP3 apoptosis down Homo sapiens esophageal carcinoma 23504349 9606 7078 HSMRK222|K222|K222TA2|SFD HGNC:11822|MIM:188826|Ensembl:ENSG00000100234|HPRD:01785|Vega:OTTHUMG00000030784 22 22q12.3 TIMP metallopeptidase inhibitor 3 protein-coding TIMP metallopeptidase inhibitor 3 miR-21 expression was increased significantly in ESCC tissues compared with NMAT. miR-21 down-regulation inhibits cell growth, cell invasion and induces cells to apoptosis. FASL, TIMP3 and RECK are direct targets of miR-21. 1326 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA TNF apoptosis Homo sapiens cardiomyocytes 23710745 9606 7124 DIF|TNF-alpha|TNFA|TNFSF2 HGNC:11892|MIM:191160|Ensembl:ENSG00000232810|HPRD:01855|Vega:OTTHUMG00000031194 6 6p21.3 tumor necrosis factor protein-coding tumor necrosis factor MicroRNA-21 reduced TNF-¦Á induced cardiomyocytes apoptosis [(23.42 ¡À 1.98)% vs. (78.37 ¡À 2.03)%, P < 0.05]. TNF-¦Á downregulated the expression of microRNA-21 and upregulated the mRNA and protein expressions of PTEN. Phosphorylation of PTEN, AKT and FOXO3a was enhanced in cardiomyocytes transfected with lenti-microRNA-21 (P < 0.05). TNF-¦Á also significantly activated the phosphorylation of PTEN, AKT and FOXO3a (P < 0.05). Compared with cardiomyocytes treated with TNF-¦Á (10 ng/ml), the phosphorylation of PTEN, AKT and FOXO3a as well as expression of pPTEN, pAKTser473, pFOXO3a and FasL were significantly suppressed in cardiomyocytes treated with lenti-microRNA-21 and TNF-¦Á (P < 0.05). Total AKT and FOXO3a were similar among all groups (P > 0.05). 1327 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA TPM1 apoptosis down Homo sapiens breast cancer cells 17363372 9606 7168 C15orf13|CMD1Y|CMH3|HTM-alpha|LVNC9|TMSA HGNC:12010|MIM:191010|Ensembl:ENSG00000140416|HPRD:01839|Vega:OTTHUMG00000132803 15 15q22.1 tropomyosin 1 (alpha) protein-coding tropomyosin 1 (alpha) alpha-tropomyosin|cardiom MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). Overexpression of TPM1 in breast cancer MCF-7 cells suppressed anchorage-independent growth. 1328 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA TPM1 apoptosis down Homo sapiens tongue squamous cell carcinomas cells 19509158 9606 7168 C15orf13|CMD1Y|CMH3|HTM-alpha|LVNC9|TMSA HGNC:12010|MIM:191010|Ensembl:ENSG00000140416|HPRD:01839|Vega:OTTHUMG00000132803 15 15q22.1 tropomyosin 1 (alpha) protein-coding tropomyosin 1 (alpha) alpha-tropomyosin|cardiom MiR-21 is an independent prognostic indicator for TSCC, and may play a role in TSCC development by inhibiting cancer cell apoptosis partly via TPM1 silencing. 1329 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA TPM1 apoptosis down Homo sapiens 23558936 9606 7168 C15orf13|CMD1Y|CMH3|HTM-alpha|LVNC9|TMSA HGNC:12010|MIM:191010|Ensembl:ENSG00000140416|HPRD:01839|Vega:OTTHUMG00000132803 15 15q22.1 tropomyosin 1 (alpha) protein-coding tropomyosin 1 (alpha) MiR-21 is overexpressed in RCC tissue and modulates the growth, apoptosis and cell cycle progression of RCC cells and regulates the expression of PDCD4 and TPM1. 1330 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA apoptosis up Homo sapiens cultured glioblastoma tumor tissue 16024602 9606 Knockdown of miR-21 in cultured glioblastoma cells triggers activation of caspases and leads to increased apoptotic cell death. 1331 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA apoptosis Homo sapiens A549 cell 18982517 9606 The results showed that AMO-miR-21, AMO-miR-16, and AMO-miR-181a inhibited A549 cell growth by inducing apoptosis and S-phase arrest. These inhibitory effects increased with dose and time. It was found that AMO-miR-21 down-regulated miR-21 expression in A549 cells. We conclude that miR-21, miR-16, and miR-181a are potential targets for lung cancer therapy, and specific AMOs can be a powerful technique for miRNA inhibition 1332 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA apoptosis Homo sapiens pancreatic cancer cells 19730150 9606 8434 ST15 HGNC:11345|MIM:605227|Ensembl:ENSG00000122707|HPRD:05567|Vega:OTTHUMG00000019898|M2D:hsa-miR-21 9 9p13.3 reversion-inducing-cysteine-rich protein with kazal motifs protein coding reversion-inducing-cysteine-rich protein with kazal motifs membrane-anchored glycopr Antisense inhibition of microRNA-21 or -221 arrests cell cycle, induces apoptosis, and sensitizes the effects of gemcitabine in pancreatic adenocarcinoma. 1333 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA apoptosis Homo sapiens 20693987 9606 When miR-21 was inactivated, the tumours regressed completely in a few days, partly as a result of apoptosis. These results demonstrate that tumours can become addicted to oncomiRs and support efforts to treat human cancers through pharmacological inactivation of miRNAs such as miR-21. 1334 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA apoptosis Homo sapiens 21139417 9606 MiR-21 is a miRNA that is overexpressed in most tumor types, and acts as an oncogene by targeting many tumor suppressor genes related to proliferation, apoptosis, and invasion. 1335 miR-21 hsa-miR-21-5p,hsa-miR-211-5p,hsa-miR-212-3p,hsa-miR-214-3p,hsa-miR-216 MIMAT0000076,MIMAT0000268,MIMAT0000269,MIMAT000027 miRNA apoptosis Homo sapiens glioblastoma cells 22528454 9606 Accumulating evidence indicated that downregulation of miR-21 in glioblastoma cells caused repression of growth and increased apoptosis, all of which could theoretically enhance the chemotherapeutic effects of cancer therapy. 1336 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA apoptosis Homo sapiens melanoma cells 22716245 9606 We show that downregulation of miR-21 in melanoma cell lines with high endogenous miR-21 expression induced apoptosis, whereas proliferation was not significantly altered. Upregulation of miR-21 in melanocytes resulted in increased proliferation and decreased apoptosis. 1337 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA apoptosis Homo sapiens right ventricular myocardial cells 22842854 9606 The TMZ-treated RVMCs showed less apoptosis and an increased expression of miR-21. 1338 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA apoptosis Homo sapiens glioma cells 22853427 9606 5728 BZS|DEC|CWS1|GLM2|MHAM|TEP1|MMAC1|PTEN1|10q23del HGNC:9588|HPRD:03431|MIM:601728 10 10q23.3 Down-regulation of microRNA-21 (miR-21) can induce cell apoptosis and reverse drug resistance in cancer treatments. 1339 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA apoptosis down Homo sapiens glioblastoma cells 22907752 9606 Silencing of hnRNPC lowered miR-21 levels, in turn increasing the expression of PDCD4, suppressing Akt and p70S6K activation, and inhibiting migratory and invasive activities. Silencing of hnRNPC reduced cell proliferation and enhanced etoposide-induced apoptosis. I 1340 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA apoptosis down Homo sapiens kidney cells 23151984 9606 Xu et al. provide new insights into the protective effects of delayed IPC and its inhibition of apoptosis by implicating a modulatory role for the microRNA miR-21. 1341 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA apoptosis down Homo sapiens Hepatocellular carcinoma cells 23232518 9606 The recombinant adenovirus inhibited the expression of miR-21 in HepG2 cells, and also depressed the proliferation of HepG2 cells and promoted the apoptosis. 1342 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA apoptosis Homo sapiens pancreatic cancer cells 23481326 9606 Targeting miR-21 for the therapy of pancreatic cancer.miR-21 depletion stopped the progression of a very aggressive model of PDA, to induce cell death by apoptosis 1343 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA apoptosis Homo sapiens atrial cell 23595377 9606 Samples of a trial tissue showed the abnormal pathohistological and ultrastructural changes, the accelerated fibrosis, and apoptosis with aging and/or in AF dogs. Compared to the adult group, the expressions of microRNAs-21 and -29 were significantly increased, whereas the expressions of microRNAs-1 and -133 showed obvious downregulation tendency in the aged group. 1344 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA apoptosis Homo sapiens pancreatic cancer cells 23726431 9606 MiR-21 levels increased in all cell lines grown in hypoxic conditions versus normoxia, whereas siRNA targeting HIF-1¦Á reduced miR-21 expression. Hypoxic conditions resulted in direct binding of HIF-1¦Á to the predicted binding site in miR-21. MiR-21 overexpression allows cells to avoid apoptosis in a hypoxic microenvironment. 1345 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA apoptosis down Homo sapiens non-small cell lung cancer cells 23777591 9606 Overexpression of miRNA-21 promotes radiation-resistance of non-small cell lung cancer.Decreased miRNA-21 expression promoted the apoptosis of A549 cells induced by irradiation. 1346 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA apoptosis down Homo sapiens colon cancer cell 24427170 9606 Recent studies showed that silencing of miR21 through use of a miR21 inhibitor (anti-miR21) affected viability, apoptosis and the cell cycle in colon cancer cells. We identified an anti-miR21 that targets miR21 to inhibit genes by both post-transcriptional gene silencing and transcriptional gene silencing in the cytoplasm and nucleus, respectively. Overexpression of anti-miR21 in colon cancer cells caused changes in miRNA expression levels. We found that treatment with anti-miR21 down-regulated expression of miR30, which is involved in angiogenesis. 1347 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA apoptosis down Homo sapiens T cell and macrophages 24577093 9606 79626 TNFAIP8L2 HGNC:26277|Ensembl:ENSG00000163154|HPRD:08029|MIM:612112|Vega:OTTHUMG00000012259 1 1q21.3 tumor necrosis factor, alpha-induced protein 8-like 2 protein coding tumor necrosis factor, alpha-induced protein 8-like 2 We report here that miR-21 is a direct target of nuclear factor-¦ÊB and could regulate Tipe2 expression in a Tipe2 coding region-dependent manner. In activated T cells and macrophages, Tipe2 expression was markedly downregulated, whereas miR-21 expression was upregulated. 1348 miR-21 hsa-miR-21-5p,hsa-miR-21-3p MIMAT0000076,MIMAT0004494 miRNA apoptosis Homo sapiens uterine cell 24706045 9606 Mounting evidence supports a functional role for miRNA as either indirect or direct regulators of gene expression which impacts the pathobiology of uterine fibroids. Specifically, miRNAs let-7, 200a, 200c, 93, 106b and 21 have been implicated in cellular proliferation, apoptosis, extracellular matrix turnover, angiogenesis and inflammation. Preliminary data provide evidence to suggest that respective in vitro miRNA expression in leiomyomata and myometrium is regulated by sex steroids. 1349 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA AIFM3 apoptosis down Homo sapiens hepatoma 22387901 9606 150209 AIFL HGNC:26398|Ensembl:ENSG00000183773|HPRD:08085|Vega:OTTHUMG00000150804 22 22q11.21 apoptosis-inducing factor, mitochondrion-associated, 3 protein-coding apoptosis-inducing factor, mitochondrion-associated, 3 Moreover, apoptosis-inducing factor, mitochondrion-associated, 3 (AIFM3) was identified as a direct target gene of miR-210. AIFM3 downregulation by siRNA attenuated radiation induced apoptosis in miR-210 downregulated hypoxic human hepatoma cells. 1350 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA BAX apoptosis down Homo sapiens pheochromocytoma cells 23591709 9606 581 BCL2L4 HGNC:959|MIM:600040|Ensembl:ENSG00000087088|HPRD:02498|Vega:OTTHUMG00000160476 19 19q13.3-q13.4 BCL2-associated X protein protein-coding BCL2-associated X protein We established an ex vivo model of HIE using oxygen-glucose deprivation (OGD) and demonstrated that miR-210 expression was upregulated in pheochromocytoma (PC12) cells after 4 h of OGD compared with normoxic controls. Furthermore, miR-210 suppressed cell apoptosis by inhibiting caspase activity and by regulating the balance between Bcl-2 and Bax levels. 1351 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA BAX apoptosis down Homo sapiens 24089674 9606 581 BCL2L4 HGNC:959|MIM:600040|Ensembl:ENSG00000087088|HPRD:02498|Vega:OTTHUMG00000160476 19 19q13.3-q13.4 BCL2-associated X protein protein-coding BCL2-associated X protein The results showed that microRNA-210, whose expression was downregulated in the brain 72?h after HI injury, suppressed neuronal apoptosis by inhibiting caspase activity and regulating the balance between bcl-2 and bax levels.Western blot analysis demonstrated that caspase-3, caspase-9, and bax protein levels were enhanced in miR-210 block rats and decreased in miR-210 overexpression rats compared to controls. In contrast, antiapoptotic bcl-2 expression behaved in an almost inverse manner 1352 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA BAX apoptosis Homo sapiens PC12 cell 25323830 9606 581 BCL2L4 HGNC:959|MIM:600040|Ensembl:ENSG00000087088|HPRD:02498|Vega:OTTHUMG00000160476 19 19q13.3-q13.4 BCL2-associated X protein protein-coding BCL2-associated X protein MiR-210 knockdown increased cell apoptosis by inducing caspase activity and regulating the balance between Bcl-2 and Bax levels. The present study demonstrated that miR-210 knockdown induced cell apoptosis using an ex vivo model of ischemic hypoxia (IH). Knockdown of miR-210 represents a potential novel therapeutic approach to combat neonatal IH. 1353 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA BCL2 apoptosis down Homo sapiens neuro 23108914 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 Application of miR-210 antisenses simultaneously alleviated OGD-involved inhibition of Bcl-2 mRNA expression. In comparison, overexpression of miR-210 synergistically diminished OGD-caused inhibition of Bcl-2 mRNA expression and consequently induced greater cellular insults. Taken together, this study shows that OGD can induce miR-210 expression through activating HIF-1¦Á. And miR-210 can mediate hypoxia-induced neural apoptosis by targeting Bcl-2. 1354 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA BCL2 apoptosis down Homo sapiens pheochromocytoma cells 23591709 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 We established an ex vivo model of HIE using oxygen-glucose deprivation (OGD) and demonstrated that miR-210 expression was upregulated in pheochromocytoma (PC12) cells after 4 h of OGD compared with normoxic controls. Furthermore, miR-210 suppressed cell apoptosis by inhibiting caspase activity and by regulating the balance between Bcl-2 and Bax levels. 1355 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA BCL2 apoptosis up Homo sapiens 24089674 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 The results showed that microRNA-210, whose expression was downregulated in the brain 72?h after HI injury, suppressed neuronal apoptosis by inhibiting caspase activity and regulating the balance between bcl-2 and bax levels.Western blot analysis demonstrated that caspase-3, caspase-9, and bax protein levels were enhanced in miR-210 block rats and decreased in miR-210 overexpression rats compared to controls. In contrast, antiapoptotic bcl-2 expression behaved in an almost inverse manner 1356 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA BCL2 apoptosis Homo sapiens PC12 cell 25323830 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 MiR-210 knockdown increased cell apoptosis by inducing caspase activity and regulating the balance between Bcl-2 and Bax levels. The present study demonstrated that miR-210 knockdown induced cell apoptosis using an ex vivo model of ischemic hypoxia (IH). Knockdown of miR-210 represents a potential novel therapeutic approach to combat neonatal IH. 1357 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA BNIP3 apoptosis down Homo sapiens neural progenitor cells 23688833 9606 664 NIP3 HGNC:1084|MIM:603293|HPRD:04482 10 10q26.3 BCL2/adenovirus E1B 19kDa interacting protein 3 protein-coding BCL2/adenovirus E1B 19kDa interacting protein 3 miR-210 suppresses BNIP3 to protect against the apoptosis of neural progenitor cells.the over-expression of miR-210 decreased apoptosis in NPCs, and the inhibition of miR-210 expression remarkably increased the number of TUNEL-positive NPCs by 30% in response to hypoxia. 1358 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA CASP3 apoptosis up Homo sapiens glioma stem cell 24930954 9606 836 CPP32|CPP32B|SCA-1 HGNC:1504|MIM:600636|Ensembl:ENSG00000164305|HPRD:02799|Vega:OTTHUMG00000133681 4 4q34 caspase 3, apoptosis-related cysteine peptidase protein-coding caspase 3, apoptosis-related cysteine peptidase Moreover, knockdown of miR-210 led to increased apoptotic rate and Caspase-3/7 activity and decreased invasive capacity, reactive oxygen species (ROS) and lactate production and radioresistance in hypoxic GSCs. These findings suggest that miR-210 might be a potential therapeutic target to eliminate GSCs located in hypoxic niches. 1359 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA CASP7 apoptosis down Homo sapiens glioma stem cell 24930954 9606 840 CASP-7|CMH-1|ICE-LAP3|LICE2|MCH3 HGNC:1508|MIM:601761|Ensembl:ENSG00000165806|HPRD:03457|Vega:OTTHUMG00000019076 10 10q25 caspase 7, apoptosis-related cysteine peptidase protein-coding caspase 7, apoptosis-related cysteine peptidase Moreover, knockdown of miR-210 led to increased apoptotic rate and Caspase-3/7 activity and decreased invasive capacity, reactive oxygen species (ROS) and lactate production and radioresistance in hypoxic GSCs. These findings suggest that miR-210 might be a potential therapeutic target to eliminate GSCs located in hypoxic niches. 1360 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA CASP8AP2 apoptosis down Homo sapiens mesenchymal stem cells 19721136 9606 9994 CED-4|FLASH|RIP25 HGNC:1510|MIM:606880|HPRD:06048 6 6q15 caspase 8 associated protein 2 protein-coding caspase 8 associated protein 2 CASP8 associated protein Induction of FLASH/CASP8AP2 in miR-210 knocked-down (PC)MSCs resulted in increased cell apoptosis. 1361 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA CASP8AP2 apoptosis down Homo sapiens stem cell 22482882 9606 9994 CED-4|FLASH|RIP25 HGNC:1510|MIM:606880|HPRD:06048 6 6q15 caspase 8 associated protein 2 protein-coding caspase 8 associated protein 2 IPC enhances stem cell survival via the combined participation of hypoxia responsive miRs miR-107 and miR-210 via their respective putative target genes Pdcd10 and Casp8ap2. 1362 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA EFNA3 apoptosis down Homo sapiens cardiomyocytic cell 25016614 9606 1944 EFL2|EPLG3|Ehk1-L|LERK3 HGNC:3223|MIM:601381|Ensembl:ENSG00000143590|HPRD:03225|Vega:OTTHUMG00000035313 1 1q21-q22 ephrin-A3 protein-coding ephrin-A3 MiR-210 down-regulated its known targets, ephrin A3 and PTP1b, inhibiting apoptosis in cardiomyocytic cells. 1363 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA FGFRL1 apoptosis down Homo sapiens laryngocarcinoma cell 25639884 9606 53834 FGFR5|FHFR HGNC:3693|MIM:605830|Ensembl:ENSG00000127418|HPRD:16163|Vega:OTTHUMG00000118998 4 4p16 fibroblast growth factor receptor-like 1 protein-coding fibroblast growth factor receptor-like 1 We found that miR-210 was highly expressed in hypoxia, which inhibited proliferation by inducing cell cycle arrest in G1/G0 as well as apoptosis. We further identified that miR-210 targeted fibroblast growth factor receptor-like 1 (FGFRL1). Down regulation of FGFRL1 decreased cell proliferation by promoting proportion of cells in G1/G0 phase and decreasing in S and G2/M phases. Moreover, overexpression of FGFRL1 effectively released the miR-210-induced suppression of SCC10A cell proliferation. Expression of miR-210 repressed tumor xenograft growth in vivo as well. Together, our findings reveal a new mechanism of adaptation to hypoxia that miR-210 inhibits the proliferation via inducing cell cycle arrest and apoptosis by the targeting of FGFRL1. 1364 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA HIF1A apoptosis Homo sapiens chondrocytes 24790587 9606 3091 HIF-1A|HIF-1alpha|HIF1|HIF1-ALPHA|MOP1|PASD8|bHLHe78 HGNC:4910|MIM:603348|Ensembl:ENSG00000100644|HPRD:04517|Vega:OTTHUMG00000140344 14 14q23.2 hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) protein-coding hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) HIF-1 ¦Á had pivotal effects on downregulation of miR-210 decreasing viability and inducing apoptosis in hypoxic chondrocytes. 1365 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA HIF1A apoptosis Homo sapiens colon cancer cell 25385144 9606 3091 HIF-1A|HIF-1alpha|HIF1|HIF1-ALPHA|MOP1|PASD8|bHLHe78 HGNC:4910|MIM:603348|Ensembl:ENSG00000100644|HPRD:04517|Vega:OTTHUMG00000140344 14 14q23.2 hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) protein-coding hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) Hypoxia-induced autophagy reduces radiosensitivity by the HIF-1¦Á/miR-210/Bcl-2 pathway in colon cancer cells.The inhibition of HIF-1¦Á decreased miR-210 expression and autophagy. Silencing of miR-210 upregulated Bcl-2 expression and reduced the survival fraction of colon cancer cells after radiation treatment. 1366 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA PTPN1 apoptosis down Homo sapiens cardiomyocytic cell 25016614 9606 5770 PTP1B HGNC:9642|MIM:176885|Ensembl:ENSG00000196396|HPRD:01477|Vega:OTTHUMG00000032729 20 20q13.1-q13.2 protein tyrosine phosphatase, non-receptor type 1 protein-coding protein tyrosine phosphatase, non-receptor type 1 MiR-210 down-regulated its known targets, ephrin A3 and PTP1b, inhibiting apoptosis in cardiomyocytic cells. 1367 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA SIN3A apoptosis down Homo sapiens glioma cell 25481483 9606 25942 - HGNC:19353|MIM:607776|Ensembl:ENSG00000169375|HPRD:09690|Vega:OTTHUMG00000142834 15 15q24.2 SIN3 transcription regulator family member A protein-coding SIN3 transcription regulator family member A miR-210 up-regulation inhibits proliferation and induces apoptosis in glioma cells by targeting SIN3A. Aberrantly expressed miR-210 regulates human U251 glioma cells apoptosis and proliferation partly through directly down-regulating SIN3A protein expression. This might offer a new potential therapeutic stratagem for glioma. 1368 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA STAT3 apoptosis up Homo sapiens endometriotic cyst stromal cell 25516558 9606 6774 APRF|HIES HGNC:11364|MIM:102582|Ensembl:ENSG00000168610|HPRD:00026|Vega:OTTHUMG00000150645 17 17q21.31 signal transducer and activator of transcription 3 (acute-phase response factor) protein-coding signal transducer and activator of transcription 3 (acute-phase response factor) Up-regulated miR-210 expression in ECSCs is involved in their proliferation, resistance to apoptosis and angiogenesis through signal transducer and activator of transcription (STAT) 3. 1369 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA TNF apoptosis Homo sapiens mesenchymal stem cell 25620256 9606 7124 DIF|TNF-alpha|TNFA|TNFSF2 HGNC:11892|MIM:191160|Ensembl:ENSG00000232810|HPRD:01855|Vega:OTTHUMG00000031194 6 6p21.3 tumor necrosis factor protein-coding tumor necrosis factor HCC Cells.MicroRNA-210 mediates the protective effect of rosuvastatin on human mesenchymal stem cells apoptosis induced by tumor necrosis factor-¦Á. 1370 miR-210 hsa-miR-210-3p,hsa-miR-210-5p MIMAT0000267,MIMAT0026475 miRNA apoptosis Homo sapiens HeLa cells 15741182 9606 We also identified miRNA that when inhibited increased the level of apoptosis (miR-1d, 7, 148, 204, 210, 216 and 296) and one miRNA that decreased apoptosis (miR-214) in HeLa cells. 1371 miR-210 hsa-miR-210-5p,hsa-miR-210-3p MIMAT0000267,MIMAT0026475 miRNA apoptosis Homo sapiens UT-7 cell 18492109 9606 A human miRNA microarray was used to analyze miRNA expression in the erythropoietin-dependent cell line UT-7/EPO compared to other factor-dependent UT-7 cell lines. Among 324 human miRNAs, MIRN188, MIRN362 and MIRN210 levels were significantly elevated in UT-7/EPO cells, and stimulation with EPO in UT-7 cells increased the level of these three miRNAs. Notably, knockdown of MIRN210 in UT-7/EPO cells led to apoptosis. 1372 miR-212 hsa-miR-212-3p,hsa-miR-212-5p MIMAT0000269,MIMAT0022695 miRNA EP300 apoptosis Homo sapiens temporal cortical areas and CA1 hippocampal neurons 23585551 9606 2033 KAT3B|RSTS2|p300 HGNC:3373|MIM:602700|Ensembl:ENSG00000100393|HPRD:04078|Vega:OTTHUMG00000150937 22 22q13.2 E1A binding protein p300 protein-coding E1A binding protein p300 we demonstrate that miR-132/212 controls cell survival by direct regulation of PTEN, FOXO3a and P300, which are all key elements of AKT signaling pathway. Silencing of these three target genes by RNAi abrogates apoptosis caused by the miR-132/212 inhibition. 1373 miR-212 hsa-miR-212-3p,hsa-miR-212-5p MIMAT0000269,MIMAT0022695 miRNA FOXO3 apoptosis Homo sapiens temporal cortical areas and CA1 hippocampal neurons 23585551 9606 2309 AF6q21|FKHRL1|FKHRL1P2|FOXO2|FOXO3A HGNC:3821|MIM:602681|Ensembl:ENSG00000118689|HPRD:04061|Vega:OTTHUMG00000015327 6 6q21 forkhead box O3 protein-coding forkhead box O3 we demonstrate that miR-132/212 controls cell survival by direct regulation of PTEN, FOXO3a and P300, which are all key elements of AKT signaling pathway. Silencing of these three target genes by RNAi abrogates apoptosis caused by the miR-132/212 inhibition. 1374 miR-212 hsa-miR-212-5p,hsa-miR-212-3p MIMAT0022695,MIMAT0000269 miRNA PEA15 apoptosis down Homo sapiens non-small cell lung cancer cells 20388802 9606 8682 HMAT1|HUMMAT1H|MAT1|MAT1H|PEA-15|PED HGNC:8822|MIM:603434|Ensembl:ENSG00000162734|HPRD:04579|Vega:OTTHUMG00000031605 1 1q21.1 phosphoprotein enriched in astrocytes 15 protein-coding phosphoprotein enriched in astrocytes 15 MiR-212 increases tumor necrosis factor-related apoptosis-inducing ligand sensitivity in non-small cell lung cancer by targeting the antiapoptotic protein PED. 1375 miR-212 hsa-miR-212-3p,hsa-miR-212-5p MIMAT0000269,MIMAT0022695 miRNA PTEN apoptosis Homo sapiens temporal cortical areas and CA1 hippocampal neurons 23585551 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog we demonstrate that miR-132/212 controls cell survival by direct regulation of PTEN, FOXO3a and P300, which are all key elements of AKT signaling pathway. Silencing of these three target genes by RNAi abrogates apoptosis caused by the miR-132/212 inhibition. 1376 miR-214 hsa-miR-214-3p,hsa-miR-214-5p MIMAT0000271,MIMAT0004564 miRNA BCL2L11 apoptosis up Homo sapiens H9c2 cell 25593579 9606 10018 BAM|BIM|BOD HGNC:994|MIM:603827|Ensembl:ENSG00000153094|HPRD:04828|Vega:OTTHUMG00000131256 2 2q13 BCL2-like 11 (apoptosis facilitator) protein-coding BCL2-like 11 (apoptosis facilitator) Transfection of miR-214 mimic showed protective effects on OGD-induced injury to H9c2 cells by reducing apoptosis, decreasing LDH and CK activities, rescuing the OGD-induced Ca(2+) and down-regulating elevated protein levels of NCX1, BIM, CaMKII¦Ä and CypD. 1377 miR-214 hsa-miR-214-3p,hsa-miR-214-5p MIMAT0000271,MIMAT0004564 miRNA BCL2L2 apoptosis down Homo sapiens cervical cancer HeLa and C-33A cell 23337879 9606 599 BCL-W|BCL2-L-2|BCLW|PPP1R51 HGNC:995|MIM:601931|Ensembl:ENSG00000129473|HPRD:03569|Vega:OTTHUMG00000028738 14 14q11.2-q12 BCL2-like 2 protein-coding BCL2-like 2 Here we demonstrate that ectopic expression of miR-214 reduces cell survival, induces apoptosis and enhances sensitivity to cisplatin through directly inhibiting Bcl2l2 expression in cervical cancer HeLa and C-33A cells. 1378 miR-214 hsa-miR-214-3p,hsa-miR-214-5p MIMAT0000271,MIMAT0004564 miRNA CAMK2A apoptosis up Homo sapiens H9c2 cell 25593579 9606 815 CAMKA HGNC:1460|MIM:114078|Ensembl:ENSG00000070808|HPRD:06532|Vega:OTTHUMG00000134281 5 5q32 calcium/calmodulin-dependent protein kinase II alpha protein-coding calcium/calmodulin-dependent protein kinase II alpha Transfection of miR-214 mimic showed protective effects on OGD-induced injury to H9c2 cells by reducing apoptosis, decreasing LDH and CK activities, rescuing the OGD-induced Ca(2+) and down-regulating elevated protein levels of NCX1, BIM, CaMKII¦Ä and CypD. 1379 miR-214 hsa-miR-214-3p,hsa-miR-214-5p MIMAT0000271,MIMAT0004564 miRNA CMPK1 apoptosis Homo sapiens H9c2 cell 25593579 9606 51727 CK|CMK|CMPK|UMK|UMP-CMPK|UMPK HGNC:18170|MIM:191710|Ensembl:ENSG00000162368|HPRD:18258|Vega:OTTHUMG00000007849 1 1p32 cytidine monophosphate (UMP-CMP) kinase 1, cytosolic protein-coding cytidine monophosphate (UMP-CMP) kinase 1, cytosolic Transfection of miR-214 mimic showed protective effects on OGD-induced injury to H9c2 cells by reducing apoptosis, decreasing LDH and CK activities, rescuing the OGD-induced Ca(2+) and down-regulating elevated protein levels of NCX1, BIM, CaMKII¦Ä and CypD. 1380 miR-214 hsa-miR-214-3p,hsa-miR-214-5p MIMAT0000271,MIMAT0004564 miRNA HDGF apoptosis down Homo sapiens human hepatocellular carcinoma cells 22613005 9606 3068 HMG1L2 HGNC:4856|MIM:600339|Ensembl:ENSG00000143321|HPRD:02079|Vega:OTTHUMG00000041295 1 1q23.1 hepatoma-derived growth factor protein-coding hepatoma-derived growth factor The genes downregulated by ectopic expression of miR-214 were involved in the regulation of apoptosis, cell cycle, and angiogenesis. Downregulation of miR-214 contributes to the unusual hypervascularity of HCC via activation of the HDGF paracrine pathway for tumor angiogenesis. 1381 miR-214 hsa-miR-214-3p,hsa-miR-214-5p MIMAT0000271,MIMAT0004564 miRNA LDHA apoptosis Homo sapiens H9c2 cell 25593579 9606 3939 GSD11|HEL-S-133P|LDH1|LDHM HGNC:6535|MIM:150000|Ensembl:ENSG00000134333|HPRD:01025|Vega:OTTHUMG00000167721 11 11p15.4 lactate dehydrogenase A protein-coding lactate dehydrogenase A Transfection of miR-214 mimic showed protective effects on OGD-induced injury to H9c2 cells by reducing apoptosis, decreasing LDH and CK activities, rescuing the OGD-induced Ca(2+) and down-regulating elevated protein levels of NCX1, BIM, CaMKII¦Ä and CypD. 1382 miR-214 hsa-miR-214-3p,hsa-miR-214-5p MIMAT0000271,MIMAT0004564 miRNA PDRG1 apoptosis down Homo sapiens bladder cancer cell 25706919 9606 81572 C20orf126|PDRG HGNC:16119|MIM:610789|Ensembl:ENSG00000088356|HPRD:17833|Vega:OTTHUMG00000032196 20 20q11.21 p53 and DNA-damage regulated 1 protein-coding p53 and DNA-damage regulated 1 Restoration of miR-214 expression in bladder cancer cell lines inhibited cell proliferation, migration, invasion and markedly promoted apoptosis. Dual-luciferase reporter assay recognized PDRG1 as direct downstream target gene of miR-214 1383 miR-214 hsa-miR-214-3p,hsa-miR-214-5p MIMAT0000271,MIMAT0004564 miRNA PPID apoptosis down Homo sapiens H9c2 cell 25593579 9606 5481 CYP-40|CYPD HGNC:9257|MIM:601753|Ensembl:ENSG00000171497|HPRD:11875|Vega:OTTHUMG00000161927 4 4q31.3 peptidylprolyl isomerase D protein-coding peptidylprolyl isomerase D Transfection of miR-214 mimic showed protective effects on OGD-induced injury to H9c2 cells by reducing apoptosis, decreasing LDH and CK activities, rescuing the OGD-induced Ca(2+) and down-regulating elevated protein levels of NCX1, BIM, CaMKII¦Ä and CypD. 1384 miR-214 hsa-miR-214-3p,hsa-miR-214-5p MIMAT0000271,MIMAT0004564 miRNA PSMD10 apoptosis down Homo sapiens myeloma 23100276 9606 5716 dJ889N15.2|p28|p28(GANK) HGNC:9555|MIM:300880|Ensembl:ENSG00000101843|HPRD:04594|Vega:OTTHUMG00000022177 X Xq22.3 proteasome (prosome, macropain) 26S subunit, non-ATPase, 10 protein-coding proteasome (prosome, macropain) 26S subunit, non-ATPase, 10 Ectopic expression of miR-214 reduced cell growth and induced apoptosis of myeloma cells.miR-214 directly down-regulated the expression of PSMD10, which encodes the oncoprotein gankyrin, and ASF1B, a histone chaperone required for DNA replication, by binding to their 3'-untranslated regions. 1385 miR-214 hsa-miR-214-5p,hsa-miR-214-3p MIMAT0004564,MIMAT0000271 miRNA PTEN apoptosis down Homo sapiens ovarian cancer cells 18199536 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog MMAC1 phosphatase and ten MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. 1386 miR-214 hsa-miR-214-5p,hsa-miR-214-3p MIMAT0004564,MIMAT0000271 miRNA PTEN apoptosis down Homo sapiens monocytes 21228352 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog Overexpression of pre-miR-214 led to impaired PTEN expression and delayed apoptosis of THP-1 cells, whereas knockdown of miR-214 level largely abolished AGE-induced cell survival. 1387 miR-214 hsa-miR-214-3p,hsa-miR-214-5p MIMAT0000271 ,MIMAT0004564 miRNA PTEN apoptosis down Homo sapiens 22929890 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog Altogether, these results show that downregulation of miRNA-214 leads to upregulation of PTEN, which subsequently reduces Akt phosphorylation. 1388 miR-214 hsa-miR-214-3p,hsa-miR-214-5p MIMAT0000271,MIMAT0004564 miRNA PTEN apoptosis Homo sapiens osteosarcoma cell 25310480 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog Overexpression of miR-214 in Saos?2 cells induced cell proliferation, while inhibition of miR-214 promoted Saos?2 cell apoptosis in vitro. Furthermore, ectopic expression of miR-214 markedly promoted osteosarcoma development in a subcutaneous xenotransplantation model in BALB/c athymic nude mice. The role of miR-214 in osteocarcinogenesis was further investigated and phosphatase and tensin homolog (PTEN) was determined to be a direct target of miR-214 in Saos?2 cells. The proliferation?promoting effect of PTEN knockdown was similar to that of miR-214 overexpression. 1389 miR-214 hsa-miR-214-3p,hsa-miR-214-5p MIMAT0000271,MIMAT0004564 miRNA SLC8A1 apoptosis down Homo sapiens H9c2 cell 25593579 9606 6546 NCX1 HGNC:11068|MIM:182305|Ensembl:ENSG00000183023|HPRD:01659 2 2p22.1 solute carrier family 8 (sodium/calcium exchanger), member 1 protein-coding solute carrier family 8 (sodium/calcium exchanger), member 1 Transfection of miR-214 mimic showed protective effects on OGD-induced injury to H9c2 cells by reducing apoptosis, decreasing LDH and CK activities, rescuing the OGD-induced Ca(2+) and down-regulating elevated protein levels of NCX1, BIM, CaMKII¦Ä and CypD. 1390 miR-214 hsa-miR-214-3p,hsa-miR-214-5p MIMAT0000271,MIMAT0004564 miRNA apoptosis Homo sapiens HeLa cells 15741182 9606 We also identified miRNA that when inhibited increased the level of apoptosis (miR-1d, 7, 148, 204, 210, 216 and 296) and one miRNA that decreased apoptosis (miR-214) in HeLa cells. 1391 miR-215 hsa-miR-192-5p,hsa-miR-192-3p MIMAT0000222,MIMAT0004543 miRNA IL17A apoptosis down Homo sapiens myeloma 25489847 9606 3605 CTLA8|IL-17|IL-17A|IL17 HGNC:5981|MIM:603149|Ensembl:ENSG00000112115|HPRD:04396|Vega:OTTHUMG00000014840 6 6p12 interleukin 17A protein-coding interleukin 17A IL-17 significantly induced cell proliferation, inhibited cellular apoptosis, repressed cell adhesion to fibronectin and collagen I, Further experiments showed that IL-17 activated the oncogenic p65 transcription factor, which directly repressed the miR-192 gene via binding to the miR-192 promoter. Loss of miR-192 in MM cells can mimic the effects of IL-17, and was required for the above oncogenic effects of IL-17 on MM. Furthermore, we found that miR-192, and its homologous miR-215 directly targeted the 3'-untranslated regions of IL-17Rs, including IL-17RA and RE mRNA. By examining bone marrow specimens derived from MM patients, a negative correlation between miR-192 expression and IL-17 or IL-17RA expression was observed. 1392 miR-215 hsa-miR-192-5p,hsa-miR-192-3p MIMAT0000222,MIMAT0004543 miRNA IL17RA apoptosis down Homo sapiens myeloma 25489847 9606 23765 CANDF5|CD217|CDw217|IL-17RA|IL17R|hIL-17R HGNC:5985|MIM:605461|Ensembl:ENSG00000177663|HPRD:10399|Vega:OTTHUMG00000150026 22 22q11.1 interleukin 17 receptor A protein-coding interleukin 17 receptor A IL-17 significantly induced cell proliferation, inhibited cellular apoptosis, repressed cell adhesion to fibronectin and collagen I, Further experiments showed that IL-17 activated the oncogenic p65 transcription factor, which directly repressed the miR-192 gene via binding to the miR-192 promoter. Loss of miR-192 in MM cells can mimic the effects of IL-17, and was required for the above oncogenic effects of IL-17 on MM. Furthermore, we found that miR-192, and its homologous miR-215 directly targeted the 3'-untranslated regions of IL-17Rs, including IL-17RA and RE mRNA. By examining bone marrow specimens derived from MM patients, a negative correlation between miR-192 expression and IL-17 or IL-17RA expression was observed. 1393 miR-215 hsa-miR-192-5p,hsa-miR-192-3p MIMAT0000222,MIMAT0004543 miRNA XIAP apoptosis down Homo sapiens non-small cell lung cancer cell 25444916 9606 331 API3|BIRC4|IAP-3|ILP1|MIHA|XLP2|hIAP-3|hIAP3 HGNC:592|MIM:300079|Ensembl:ENSG00000101966|HPRD:02094|Vega:OTTHUMG00000022336 X Xq25 X-linked inhibitor of apoptosis protein-coding X-linked inhibitor of apoptosis Taken together, this study highlights that the proapoptotic effects of curcumin depend on miR-192-5p/215 induction and the p53-miR-192-5p/215-XIAP pathway is an important therapeutic target for non-small cell lung cancer. 1394 miR-215 hsa-miR-192-5p,hsa-miR-192-3p MIMAT0000222,MIMAT0004543 miRNA apoptosis Homo sapiens colon cancer cells 22469014 9606 protein coding In vitro analyses showed that ectopic expression of miR-215 decreases viability and migration, increases apoptosis and promotes cell cycle arrest in DLD-1 and HCT-116 colon cancer cell lines. 1395 miR-216 hsa-miR-216a-5p,hsa-miR-216a-3p,hsa-miR-216b-5p,hsa-miR-216b-5p MIMAT0000273,MIMAT0022844,MIMAT0004959,MIMAT0026721 miRNA apoptosis Homo sapiens HeLa cells 15741182 9606 We also identified miRNA that when inhibited increased the level of apoptosis (miR-1d, 7, 148, 204, 210, 216 and 296) and one miRNA that decreased apoptosis (miR-214) in HeLa cells. 1396 miR-216a hsa-miR-216a-5p,hsa-miR-216a-3p MIMAT0000273,MIMAT0022844 miRNA BIRC5 apoptosis down Homo sapiens pancreatic cancer cell 25220761 9606 332 API4|EPR-1 HGNC:593|MIM:603352|Ensembl:ENSG00000089685|HPRD:04520|Vega:OTTHUMG00000177505 17 17q25 baculoviral IAP repeat containing 5 protein-coding baculoviral IAP repeat containing 5 Treatment of pancreatic cancer cells with miR-216a significantly inhibited cell growth and promoted cell apoptosis. In addition, the downstream genes of JAK2/STAT3, survivin and X-linked inhibitor of apoptosis protein, which are anti?apoptotic genes, were also decreased by miR-216a. 1397 miR-216a hsa-miR-216a-5p,hsa-miR-216a-3p MIMAT0000273,MIMAT0022844 miRNA EIF4B apoptosis Homo sapiens non-small-cell lung cancercell 24958806 9606 1975 EIF-4B|PRO1843 HGNC:3285|MIM:603928|Ensembl:ENSG00000063046|HPRD:04892|Vega:OTTHUMG00000169570 12 12q13.13 eukaryotic translation initiation factor 4B protein-coding eukaryotic translation initiation factor 4B Our data also show that overexpression of miR216a suppresses NSCLC cell growth and metastasis, and enhances cisplatin-induced cell growth inhibition and apoptosis. In contrast, inhibition of miR216a stimulates NSCLC cell growth and metastasis, and suppresses cisplatin-induced cell growth inhibition and apoptosis. Furthermore, we demonstrate that miR216a exerts its role by directly targeting eIF4B and ZEB1. 1398 miR-216a hsa-miR-216a-5p,hsa-miR-216a-3p MIMAT0000273,MIMAT0022844 miRNA JAK2 apoptosis down Homo sapiens pancreatic cancer cell 25220761 9606 3717 JTK10|THCYT3 HGNC:6192|MIM:147796|Ensembl:ENSG00000096968|HPRD:00993|Vega:OTTHUMG00000019490 9 9p24 Janus kinase 2 protein-coding Janus kinase 2 Treatment of pancreatic cancer cells with miR-216a significantly inhibited cell growth and promoted cell apoptosis. In addition, the downstream genes of JAK2/STAT3, survivin and X-linked inhibitor of apoptosis protein, which are anti?apoptotic genes, were also decreased by miR-216a. 1399 miR-216a hsa-miR-216a-5p,hsa-miR-216a-3p MIMAT0000273,MIMAT0022844 miRNA STAT3 apoptosis down Homo sapiens pancreatic cancer cell 25220761 9606 6774 APRF|HIES HGNC:11364|MIM:102582|Ensembl:ENSG00000168610|HPRD:00026|Vega:OTTHUMG00000150645 17 17q21.31 signal transducer and activator of transcription 3 (acute-phase response factor) protein-coding signal transducer and activator of transcription 3 (acute-phase response factor) Treatment of pancreatic cancer cells with miR-216a significantly inhibited cell growth and promoted cell apoptosis. In addition, the downstream genes of JAK2/STAT3, survivin and X-linked inhibitor of apoptosis protein, which are anti?apoptotic genes, were also decreased by miR-216a. 1400 miR-216a hsa-miR-216a-5p,hsa-miR-216a-3p MIMAT0000273,MIMAT0022844 miRNA XIAP apoptosis down Homo sapiens pancreatic cancer cell 25220761 9606 331 API3|BIRC4|IAP-3|ILP1|MIHA|XLP2|hIAP-3|hIAP3 HGNC:592|MIM:300079|Ensembl:ENSG00000101966|HPRD:02094|Vega:OTTHUMG00000022336 X Xq25 X-linked inhibitor of apoptosis protein-coding X-linked inhibitor of apoptosis Treatment of pancreatic cancer cells with miR-216a significantly inhibited cell growth and promoted cell apoptosis. In addition, the downstream genes of JAK2/STAT3, survivin and X-linked inhibitor of apoptosis protein, which are anti?apoptotic genes, were also decreased by miR-216a. 1401 miR-216a hsa-miR-216a-5p,hsa-miR-216a-3p MIMAT0000273,MIMAT0022844 miRNA ZEB1 apoptosis Homo sapiens non-small-cell lung cancercell 24958806 9606 6935 AREB6|BZP|DELTAEF1|FECD6|NIL2A|PPCD3|TCF8|ZFHEP|ZFHX1A HGNC:11642|MIM:189909|Ensembl:ENSG00000148516|HPRD:01798|Vega:OTTHUMG00000017907 10 10p11.2 zinc finger E-box binding homeobox 1 protein-coding zinc finger E-box binding homeobox 1 Our data also show that overexpression of miR216a suppresses NSCLC cell growth and metastasis, and enhances cisplatin-induced cell growth inhibition and apoptosis. In contrast, inhibition of miR216a stimulates NSCLC cell growth and metastasis, and suppresses cisplatin-induced cell growth inhibition and apoptosis. Furthermore, we demonstrate that miR216a exerts its role by directly targeting eIF4B and ZEB1. 1402 miR-216b hsa-miR-216b-5p,hsa-miR-216b-5p MIMAT0004959,MIMAT0026721 miRNA P2RX7 apoptosis down Homo sapiens breast cancer cell 25078617 9606 5027 P2X7 HGNC:8537|MIM:602566|Ensembl:ENSG00000089041|HPRD:03977 12 12q24 purinergic receptor P2X, ligand-gated ion channel, 7 protein-coding purinergic receptor P2X, ligand-gated ion channel, 7 Ectopic expression of miR-216b mimics leads to inhibited cell growth and apoptosis, while blocking expression of the miR-216b results in increased cell proliferation. Furthermore, our findings demonstrate that knockdown of P2X7R promotes apoptosis in breast cancer cells through down-regulating Bcl-2 and increasing the cleavage caspase-3 protein level. Finally, we confirmed that down-regulation of miR-216b in breast cancer is inversely associated with P2X7R expression level. 1403 miR-217 hsa-miR-217 MIMAT0000274 miRNA KRAS apoptosis Homo sapiens lung cancer 25234467 9606 3845 C-K-RAS|CFC2|K-RAS2A|K-RAS2B|K-RAS4A|K-RAS4B|KI-RAS|KRAS1|KRAS2|NS|NS3|RASK2 HGNC:6407|MIM:190070|Ensembl:ENSG00000133703|HPRD:01817|Vega:OTTHUMG00000171193 12 12p12.1 Kirsten rat sarcoma viral oncogene homolog protein-coding Kirsten rat sarcoma viral oncogene homolog The effects of miR-217 overexpression on the proliferation, apoptosis, migration and invasion of SPC-A-1 and A549 cells were investigated. The target gene of miR-217 was predicted by Targetscan online software, screened by dual luciferase reporter gene assay and demonstrated by Western blot. Finally, the effects of miR-217 up-regulation on the sensitivity of A549 cells to cisplatin were determined. The expression of miR-217 was significantly lower in lung cancer tissues than in noncancerous tissues (p < 0.001). The overexpression of miR-217 significantly inhibited the proliferation, migration and invasion as well as promoted the apoptosis of lung cancer cells by targeting KRAS. The up-regulation of miR-217 enhanced the sensitivity of SPC-A-1 and A549 cells to cisplatin. In conclusion, miR-217 suppresses tumour development in lung cancer by targeting KRAS and enhances cell sensitivity to cisplatin. Our results encourage researchers to use cisplatin in combination with miR-217 to treat lung cancer. 1404 miR-218 hsa-miR-218-5p,hsa-miR-218-1-3p,hsa-miR-218-2-3p MIMAT0000275,MIMAT0004565,MIMAT0004566 miRNA AKT1 apoptosis Homo sapiens GIST cell 24706111 9606 207 AKT|CWS6|PKB|PKB-ALPHA|PRKBA|RAC|RAC-ALPHA HGNC:391|MIM:164730|Ensembl:ENSG00000142208|HPRD:01261|Vega:OTTHUMG00000170795 14 14q32.32 v-akt murine thymoma viral oncogene homolog 1 protein-coding v-akt murine thymoma viral oncogene homolog 1 The expression of miR-218 is down-regulated in an imatinib mesylate-resistant GIST cell line (GIST430), whereas miR-218 over-expression can improve the sensitivity of GIST cells to imatinib mesylate, with PI3K/AKT signaling pathway possibly involved in the mechanism. 1405 miR-218 hsa-miR-218-5p,hsa-miR-218-1-3p,hsa-miR-218-2-3p MIMAT0000275,MIMAT0004565,MIMAT0004566 miRNA BMI1 apoptosis down Homo sapiens colon cancer 23255074 9606 648 FLVI2/BMI1|PCGF4|RNF51 HGNC:1066|MIM:164831|Ensembl:ENSG00000168283|HPRD:01277|Vega:OTTHUMG00000017807 10 10p11.23 BMI1 proto-oncogene, polycomb ring finger protein-coding BMI1 proto-oncogene, polycomb ring finger MicroRNA-218 inhibits cell cycle progression and promotes apoptosis in colon cancer by downregulating BMI1 polycomb ring finger oncogene. 1406 miR-218 hsa-miR-218-5p,hsa-miR-218-1-3p,hsa-miR-218-2-3p MIMAT0000275,MIMAT0004565,MIMAT0004566 miRNA BMI1 apoptosis down Homo sapiens epatocellular carcinoma (HCC) cell 23996750 9606 648 FLVI2/BMI1|PCGF4|RNF51 HGNC:1066|MIM:164831|Ensembl:ENSG00000168283|HPRD:01277|Vega:OTTHUMG00000017807 10 10p11.23 BMI1 proto-oncogene, polycomb ring finger protein-coding BMI1 proto-oncogene, polycomb ring finger Ectopic expression of miR-218 in HepG2 cells resulted in suppressed cell proliferation and enhanced cell apoptosis as well as the down-regulation of Bmi-1 and CDK6 mRNA and protein expressions (P<0.05). 1407 miR-218 hsa-miR-218-5p,hsa-miR-218-1-3p,hsa-miR-218-2-3p MIMAT0000275,MIMAT0004565,MIMAT0004566 miRNA BRCA1 apoptosis down Homo sapiens breast cancer cell 25394901 9606 672 BRCAI|BRCC1|BROVCA1|IRIS|PNCA4|PPP1R53|PSCP|RNF53 HGNC:1100|MIM:113705|Ensembl:ENSG00000012048|HPRD:00218|Vega:OTTHUMG00000157426 17 17q21 breast cancer 1, early onset protein-coding breast cancer 1, early onset In vivo assay also demonstrated that restoring miR-218 expression in MCF-7/DDP cell line could sensitize cells against cisplatin, thereby increasing cisplatin-mediated tumor cell apoptosis and reducing DNA repair. Kaplan-Meier survival analysis indicated that patients with breast cancer display high levels of miR-218 and low levels of BRCA1 expression; these patients may gain the greatest benefits in terms of increased survival when treated with cisplatin. All of these results indicated that miR-218 has a significant function in the development of cisplatin resistance in breast cancer. Restoring miR-218 expression may constitute a novel therapeutic approach by which to increase cisplatin sensitivity in breast cancer. 1408 miR-218 hsa-miR-218-5p,hsa-miR-218-1-3p,hsa-miR-218-2-3p MIMAT0000275,MIMAT0004565,MIMAT0004566 miRNA CDK6 apoptosis Homo sapiens glioma cell 22088371 9606 1021 PLSTIRE HGNC:1777|MIM:603368|Ensembl:ENSG00000105810|HPRD:04533|Vega:OTTHUMG00000131697 7 7q21-q22 cyclin-dependent kinase 6 protein-coding cyclin-dependent kinase 6 Introducing exogenous miR-218 may effectively down-regulate the CDK6 expression, inhibit cell proliferation and induce apoptosis of malignant giloma cells. These findings imply that miR-218 may serve as a therapeutic agent against malignant glioma. 1409 miR-218 hsa-miR-218-5p,hsa-miR-218-1-3p,hsa-miR-218-2-3p MIMAT0000275,MIMAT0004565,MIMAT0004566 miRNA CDK6 apoptosis down Homo sapiens epatocellular carcinoma (HCC) cell 23996750 9606 1021 PLSTIRE HGNC:1777|MIM:603368|Ensembl:ENSG00000105810|HPRD:04533|Vega:OTTHUMG00000131697 7 7q21-q22 cyclin-dependent kinase 6 protein-coding cyclin-dependent kinase 6 Ectopic expression of miR-218 in HepG2 cells resulted in suppressed cell proliferation and enhanced cell apoptosis as well as the down-regulation of Bmi-1 and CDK6 mRNA and protein expressions (P<0.05). 1410 miR-218 hsa-miR-218-5p,hsa-miR-218-1-3p,hsa-miR-218-2-3p MIMAT0000275,MIMAT0004565,MIMAT0004566 miRNA KIT apoptosis down Homo sapiens gastrointestinal stromal tumor?cell 24375253 9606 3815 C-Kit|CD117|PBT|SCFR HGNC:6342|MIM:164920|Ensembl:ENSG00000157404|HPRD:01287|Vega:OTTHUMG00000128713 4 4q12 v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog protein-coding v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog The effect of miR-218 on the proliferation and apoptosis of GIST-T1 cell was analyzed using flow cytometry. Transwell invasion chamber was applied to detect the effect of miR-218 on the invasion of GIST-T1 cells. KIT was identified to be a target gene of miR-218 by the luciferase reporter enzyme system, and the effect of miR-218 on the expression of KIT protein in cells was determined using Western blotting. 1411 miR-218 hsa-miR-218-5p,hsa-miR-218-1-3p,hsa-miR-218-2-3p MIMAT0000275,MIMAT0004565,MIMAT0004566 miRNA PIK3CA apoptosis Homo sapiens GIST cell 24706111 9606 5290 CLOVE|CWS5|MCAP|MCM|MCMTC|PI3K|p110-alpha HGNC:8975|MIM:171834|HPRD:01382 3 3q26.3 phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha protein-coding phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha The expression of miR-218 is down-regulated in an imatinib mesylate-resistant GIST cell line (GIST430), whereas miR-218 over-expression can improve the sensitivity of GIST cells to imatinib mesylate, with PI3K/AKT signaling pathway possibly involved in the mechanism. 1412 miR-218 hsa-miR-218-5p,hsa-miR-218-1-3p,hsa-miR-218-2-3p MIMAT0000275,MIMAT0004565,MIMAT0004566 miRNA TPD52 apoptosis Homo sapiens prostate cancer cell 25511701 9606 7163 D52|N8L|PC-1|PrLZ|hD52 HGNC:12005|MIM:604068|Ensembl:ENSG00000076554|HPRD:04963|Vega:OTTHUMG00000164565 8 8q21.13 tumor protein D52 protein-coding tumor protein D52 Based on gain and loss of function analysis, we found miR-218 significantly inhibit cancer cell proliferation by inducing apoptosis. These results strongly suggest that miR-218 plays a tumor suppressor role in PC cells. In addition, our data firstly demonstrated that miR-218 directly regulates oncogenic TPD52 in PC3 cells and the miR-218-TPD52 axis can regulate growth of this prostate cancer cell line. 1413 miR-218 hsa-miR-218-5p,hsa-miR-218-1-3p,hsa-miR-218-2-3p MIMAT0000275,MIMAT0004565,MIMAT0004566 miRNA apoptosis Homo sapiens cervical cancer cells 23443110 9606 Overexpression of miR-218 reduced the proliferation of the human cervical cancer cell line HeLa and induced cell apoptosis through the AKT-mTOR signaling pathway. 1414 miR-218 hsa-miR-218-5p,hsa-miR-218-1-3p,hsa-miR-218-2-3p MIMAT0000275,MIMAT0004565,MIMAT0004566 miRNA apoptosis Homo sapiens cervical cancer cell 24843318 9606 Upregulation of miR-218 significantly enhanced the radiation-induced apoptosis, which was further enhanced by the combination of miR-218 overexpression and radiation In xenograft growth assay, combination of miR-218 overexpression and radiation notably induced cellular apoptosis and suppressed tumor growth. In conclusion, we demonstrated that miR-218 resensitized cervical cancer cells to radiation via promoting cellular apoptosis. Moreover, we proved that miR-218 as a potent predictor of radiosensitivity in cervical cancer, especially for those patients with loss of miR-218. 1415 miR-218 hsa-miR-218-5p,hsa-miR-218-1-3p,hsa-miR-218-2-3p MIMAT0000275,MIMAT0004565,MIMAT0004566 miRNA apoptosis Homo sapiens liver cancer cell 25416134 9606 Traditional Chinese medicine is recently emerged as anti-cancer therapy or adjuvant with reduced side-effects and improved quality of life. In the present study, an active ingredient, 1,6,7-trihydroxyxanthone (THA), derived from Goodyera oblongifolia was found to strongly suppress cell growth and induce apoptosis in liver cancer cells. MicroRNAs are a group of small non-coding RNAs that regulate gene expression at post-transcriptional levels. Our results demonstrated that miR-218 was up-regulated and oncogene Bmi-1 was down-regulated by THA treatment. Further investigation showed that THA-induced-miR-218 up-regulation could lead to activation of tumor suppressor P16(Ink4a) and P14(ARF), the main down-stream targets of Bmi-1. In conclusion, THA might be a potential anti-cancer drug candidate, at least in part, through the activation of miR-218 and suppression of Bmi-1 expression. 1416 miR-218 hsa-miR-218-5p,hsa-miR-218-1-3p,hsa-miR-218-2-3p MIMAT0000275,MIMAT0004565,MIMAT0004566 miRNA apoptosis Homo sapiens osteosarcoma cell 25479631 9606 The low-expression of miR-218 is correlated with the poor clinicopathological features in osteosarcoma. Moreover, miR-218 overexpression reduces cancer cell proliferation and induces apoptosis in Saos-2 cells, suggesting that miR-218 may play a key role in the progression of human osteosarcoma. 1417 miR-219 hsa-miR-219a-5p,hsa-miR-219a-1-3p,hsa-miR-219a-2-3p MIMAT0000276,MIMAT0004567,MIMAT0004675 miRNA apoptosis Homo sapiens breast cancer cells 23813567 9606 Overexpression of miR-219 in MCF-7 breast cancer cells resulted in accentuated expression of apoptosis- and proliferation-related anti-viral immunodulators of the Jak-STAT and NF-°ÙÉÇ pathways. 1418 miR-219 hsa-miR-219a-5p,hsa-miR-219a-1-3p,hsa-miR-219a-2-3p MIMAT0000276,MIMAT0004567,MIMAT0004675 miRNA apoptosis Homo sapiens 25069442 9606 In particular, the miR-219 transfection increased astrocyte viability, growth, and differentiation while decreasing cell necrosis and apoptosis. Thus, microRNA-219 transfection is a valuable strategy in order to confer resistance to astrocytes towards lymphocyte-induced neurotoxici-ty especially in the presence of IFN-alpha, whose levels are typically increased in the cerebrospinal fluid of AGS patients. 1419 miR-219-5p hsa-miR-219a-5p,hsa-miR-219a-1-3p,hsa-miR-219a-2-3p MIMAT0000276,MIMAT0004567,MIMAT0004675 miRNA ESR1 apoptosis down Homo sapiens Papillary thyroid carcinoma cell 25423566 9606 2099 ER|ESR|ESRA|ESTRR|Era|NR3A1 HGNC:3467|MIM:133430|Ensembl:ENSG00000091831|HPRD:00589|Vega:OTTHUMG00000016103 6 6q25.1 estrogen receptor 1 protein-coding estrogen receptor 1 The current study confirmed that miR-219-5p expression was inhibited in PTC tissue samples. There were statistically significant differences in the expression of miR-219-5p with regard to sex, tumor size, and lymph node metastasis in patients with PTC. Forced expression of miR-219-5p suppressed PTC cell proliferation and migration and promoted apoptosis. Further study showed that estrogen receptor (ER) ¦Á was the direct target of miR-219-5p and mediated the effect of miR-219-5p on PTC occurrence. Expression of miR-219-5p was inversely correlated with that of ER¦Á. Importantly, ER¦Á overexpression in PTC cells rescued the inhibitory effect of miR-219-5p on PTC cell proliferation and migration. 1420 miR-219-5p hsa-miR-219a-5p,hsa-miR-219a-1-3p,hsa-miR-219a-2-3p MIMAT0000276,MIMAT0004567,MIMAT0004675 miRNA MT1F apoptosis Homo sapiens 24974767 9606 4494 MT1 HGNC:7398|MIM:156352|Ensembl:ENSG00000198417|HPRD:01127 16 16q13 metallothionein 1F protein-coding metallothionein 1F Network analysis were further conducted on mRNA-miRNA pairs, which revealed that miR-219-5p-MT1F and -TRIB3 pairs by AgNPs are being involved in various cellular processes, such as, oxidative stress, cell cycle and apoptosis. 1421 miR-219-5p hsa-miR-219a-5p,hsa-miR-219a-1-3p,hsa-miR-219a-2-3p MIMAT0000276,MIMAT0004567,MIMAT0004675 miRNA TRIB3 apoptosis Homo sapiens 24974767 9606 57761 C20orf97|NIPK|SINK|SKIP3|TRB3 HGNC:16228|MIM:607898|Ensembl:ENSG00000101255|HPRD:09836|Vega:OTTHUMG00000031627 20 20p13-p12.2 tribbles pseudokinase 3 protein-coding tribbles pseudokinase 3 Network analysis were further conducted on mRNA-miRNA pairs, which revealed that miR-219-5p-MT1F and -TRIB3 pairs by AgNPs are being involved in various cellular processes, such as, oxidative stress, cell cycle and apoptosis. 1422 miR-22 hsa-miR-22-5p,hsa-miR-22-3p MIMAT0004495,MIMAT0000077 miRNA MAPK14 apoptosis down Homo sapiens brain cells 23349832 9606 1432 CSBP|CSBP1|CSBP2|CSPB1|EXIP|Mxi2|PRKM14|PRKM15|RK|SAPK2A|p38|p38ALPHA HGNC:6876|MIM:600289|Ensembl:ENSG00000112062|HPRD:02619|Vega:OTTHUMG00000159806 6 6p21.3-p21.2 mitogen-activated protein kinase 14 protein-coding mitogen-activated protein kinase 14 The mechanisms underlying the effects of miR-22 included a reduction in caspase activation, consistent with miR-22's targeting the pro-apoptotic activities of mitogen-activated protein kinase 14/p38 (MAPK14/p38) and tumor protein p53-inducible nuclear protein 1 (Tp53inp1). These data show that miR-22 has multipartite anti-neurodegenerative activities including the inhibition of apoptosis and the targeting of mRNAs implicated in the etiology of HD. 1423 miR-22 hsa-miR-22-5p,hsa-miR-22-3p MIMAT0004495,MIMAT0000077 miRNA MECOM apoptosis down Homo sapiens ovarian cancer cell 20081105 9606 2122 AML1-EVI-1|EVI1|MDS1|MDS1-EVI1|PRDM3 HGNC:3498|MIM:165215|Ensembl:ENSG00000085276|HPRD:01310|Vega:OTTHUMG00000158596 3 3q26.2 MDS1 and EVI1 complex locus protein-coding MDS1 and EVI1 complex locus Furthermore, overexpression of the putative tumor suppressor mir-22 repressed the EVI1 oncogene, which is known to suppress apoptosis by stimulating phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog 1 signaling. 1424 miR-22 hsa-miR-22-5p,hsa-miR-22-3p MIMAT0004495,MIMAT0000077 miRNA PTEN apoptosis down Homo sapiens bronchial epithelial cells 20170724 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog MiR-22 functions as a micro-oncogene that can invert the functionality of PTEN. 1425 miR-22 hsa-miR-22-5p,hsa-miR-22-3p MIMAT0004495,MIMAT0000077 miRNA RAD51 apoptosis up Homo sapiens esophageal squamous cells 23188185 9606 5888 BRCC5|HRAD51|HsRad51|HsT16930|MRMV2|RAD51A|RECA HGNC:9817|MIM:179617|Ensembl:ENSG00000051180|HPRD:01557|Vega:OTTHUMG00000130067 15 15q15.1 RAD51 recombinase protein-coding RAD51 recombinase Increased expression of miRNA-22 sensitized ESCC cells to ¦Ã-ray radiation and promoted the apoptosis of ESCC cells induced by ¦Ã-ray radiation. Increased expression level of miRNA-22 had effects on Rad51 expression after irradiation. 1426 miR-22 hsa-miR-22-5p,hsa-miR-22-3p MIMAT0004495,MIMAT0000077 miRNA TP53INP1 apoptosis down Homo sapiens 23349832 9606 94241 SIP|TP53DINP1|TP53INP1A|TP53INP1B|Teap|p53DINP1 HGNC:18022|MIM:606185|Ensembl:ENSG00000164938|HPRD:09367|Vega:OTTHUMG00000164697 8 8q22 tumor protein p53 inducible nuclear protein 1 protein-coding tumor protein p53 inducible nuclear protein 1 The mechanisms underlying the effects of miR-22 included a reduction in caspase activation, consistent with miR-22's targeting the pro-apoptotic activities of mitogen-activated protein kinase 14/p38 (MAPK14/p38) and tumor protein p53-inducible nuclear protein 1 (Tp53inp1). These data show that miR-22 has multipartite anti-neurodegenerative activities including the inhibition of apoptosis and the targeting of mRNAs implicated in the etiology of HD. 1427 miR-22 hsa-miR-22-5p,hsa-miR-22-3p MIMAT0004495,MIMAT0000077 miRNA apoptosis down Homo sapiens DAOY cell 24576181 9606 347734 SLL|SLC35B2|UGTrel4 HGNC:16872|Ensembl:ENSG00000157593|HPRD:11576|MIM:610788|Vega:OTTHUMG00000014760 6 6p12.1-p11.2 solute carrier family 35 (adenosine 3'-phospho 5'-phosphosulfate transporter), member B2 protein coding solute carrier family 35 (adenosine 3'-phospho 5'-phosphosulfate transporter), member B2 Microarray analysis in DAOY cells with forced miR-22 expression showed significant changes in expression profiles, PAPST1 being the most significantly (10 folds) downregulated gene. 1428 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA BAX apoptosis up Homo sapiens bladder cancer cell 25585941 9606 581 BCL2L4 HGNC:959|MIM:600040|Ensembl:ENSG00000087088|HPRD:02498|Vega:OTTHUMG00000160476 19 19q13.3-q13.4 BCL2-associated X protein protein-coding BCL2-associated X protein In this study, miR?221 inhibitor was transfected into bladder cancer cell lines 5637, J82 and T24 to repress the expression of miR?221. As a result, the repression of miR?221 on p53 upregulated modulator of apoptosis (PUMA) was abolished, resulting in increased expression of the pro-apoptotic Bax and reduced expression of the anti-apoptotic Bcl-2, which promotes apoptosis of bladder cancer cells. 1429 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA BBC3 apoptosis down Homo sapiens glioblastoma cells 20813046 9606 27113 JFY-1|JFY1|PUMA HGNC:17868|MIM:605854|Ensembl:ENSG00000105327|HPRD:16165|Vega:OTTHUMG00000183489 19 19q13.3-q13.4 BCL2 binding component 3 protein-coding BCL2 binding component 3 bcl-2-binding component 3 Here we showed that miR-221/222 inhibited cell apoptosis by targeting pro-apoptotic gene PUMA in human glioma cells. Enforced expression of miR-22/222 induced cell survival whereas knockdown of miR-221/222 rendered cells to apoptosis. 1430 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA BBC3 apoptosis Homo sapiens epithelial cancer cell 21042732 9606 27113 JFY-1|JFY1|PUMA HGNC:17868|MIM:605854|Ensembl:ENSG00000105327|HPRD:16165|Vega:OTTHUMG00000183489 19 19q13.3-q13.4 BCL2 binding component 3 protein-coding BCL2 binding component 3 Bioinformatics and luciferase reporter assays showed that miR-221/222 co-modulated the p53 upregulated modulator of apoptosis (PUMA) expression by directly targeting the binding site within the 3'UTR. Together, these findings suggest that PUMA is a direct target of miR-221/222 that functions as an endogenous apoptosis regulator in these epithelial cancers. 1431 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA BCL2 apoptosis down Homo sapiens bladder cancer cell 25585941 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 In this study, miR?221 inhibitor was transfected into bladder cancer cell lines 5637, J82 and T24 to repress the expression of miR?221. As a result, the repression of miR?221 on p53 upregulated modulator of apoptosis (PUMA) was abolished, resulting in increased expression of the pro-apoptotic Bax and reduced expression of the anti-apoptotic Bcl-2, which promotes apoptosis of bladder cancer cells. 1432 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA BCL2 apoptosis down Homo sapiens bladder cancer cell 25585941 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 In this study, miR?221 inhibitor was transfected into bladder cancer cell lines 5637, J82 and T24 to repress the expression of miR?221. As a result, the repression of miR?221 on p53 upregulated modulator of apoptosis (PUMA) was abolished, resulting in increased expression of the pro-apoptotic Bax and reduced expression of the anti-apoptotic Bcl-2, which promotes apoptosis of bladder cancer cells. 1433 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA BMF apoptosis down Homo sapiens hepatocellular carcinoma cells 19671867 9606 90427 - HGNC:24132|MIM:606266|Ensembl:ENSG00000104081|HPRD:05881|Vega:OTTHUMG00000129875 15 15q14 Bcl2 modifying factor protein-coding Bcl2 modifying factor bcl-2-modifying factor The analysis of HCC tissues revealed an inverse correlation between miR-221 and Bmf expression and a direct correlation between Bmf and activated caspase-3, as a marker of apoptosis. 1434 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA CASP3 apoptosis Homo sapiens bladder cancer cell 19767219 9606 836 CPP32|CPP32B|SCA-1 HGNC:1504|MIM:600636|Ensembl:ENSG00000164305|HPRD:02799|Vega:OTTHUMG00000133681 4 4q34 caspase 3, apoptosis-related cysteine peptidase protein-coding caspase 3, apoptosis-related cysteine peptidase Human miRNA-221 was significantly up-regulated in bladder cancer T24 cells and RT4 cells compared to human normal urothelial cells. T24 cell was TRAIL-resistant cell line. MiRNA-221 silencing predisposed T24 cells to undergo apoptosis induced by TRAIL and resulted in an up-modulation of cyclin-dependent kinase inhibitor p27Kip1. MiRNA-221 suppression promoted the activation of caspase 3 induced by TRAIL in T24 cells. 1435 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA CASP3 apoptosis Homo sapiens HepG2 cell 22152314 9606 836 CPP32|CPP32B|SCA-1 HGNC:1504|MIM:600636|Ensembl:ENSG00000164305|HPRD:02799|Vega:OTTHUMG00000133681 4 4q34 caspase 3, apoptosis-related cysteine peptidase protein-coding caspase 3, apoptosis-related cysteine peptidase The result from Apo-ONE homogeneous caspase-3/7 kit was consistent with the above two apoptotic assays, which showed that with miR-221 inhibitors, the activity of caspase-3/7 was significantly enhanced (P is less than to 0.05). 1436 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA CASP3 apoptosis down Homo sapiens 24969479 9606 836 CPP32|CPP32B|SCA-1 HGNC:1504|MIM:600636|Ensembl:ENSG00000164305|HPRD:02799|Vega:OTTHUMG00000133681 4 4q34 caspase 3, apoptosis-related cysteine peptidase protein-coding caspase 3, apoptosis-related cysteine peptidase As a result, we conclude that miR-221 may have a crucial role in repressing the expression of caspase-3 which may contribute to a lower apoptotic rate, thus supporting the selection of more aggressive cancer cells. To our knowledge, this is the first study related to the expression levels of caspase-3 and miR-221 in different cell lines at the same time. We expect that our study might pave the way for better understanding the role of miR-221 in apoptotic regulation of caspase-3. 1437 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA CASP7 apoptosis Homo sapiens HepG2 cell 22152314 9606 840 CASP-7|CMH-1|ICE-LAP3|LICE2|MCH3 HGNC:1508|MIM:601761|Ensembl:ENSG00000165806|HPRD:03457|Vega:OTTHUMG00000019076 10 10q25 caspase 7, apoptosis-related cysteine peptidase protein-coding caspase 7, apoptosis-related cysteine peptidase The result from Apo-ONE homogeneous caspase-3/7 kit was consistent with the above two apoptotic assays, which showed that with miR-221 inhibitors, the activity of caspase-3/7 was significantly enhanced (P is less than to 0.05). 1438 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA CDH1 apoptosis Homo sapiens breast cancer cell 23637992 9606 999 Arc-1|CD324|CDHE|ECAD|LCAM|UVO HGNC:1748|MIM:192090|Ensembl:ENSG00000039068|HPRD:01885|Vega:OTTHUMG00000137561 16 16q22.1 cadherin 1, type 1, E-cadherin (epithelial) protein-coding cadherin 1, type 1, E-cadherin (epithelial) MiR-221 knockdown not only blocked cell cycle progression, induced cell apoptosis, and inhibited cell proliferation in-vitro but it also inhibited in-vivo tumor growth by targeting p27(kip1). Furthermore, miR-221 knockdown inhibited cell migration and invasion by altering E-cadherin expression, and its regulatory transcription factors Snail and Slug in human TNBC cell lines. Therefore, miR-221 functions as an oncogene and is essential in regulating tumorigenesis in TNBCs both in vitro as well as in vivo. 1439 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA CDKN1B apoptosis down Homo sapiens lung cancer cells 18246122 9606 1027 CDKN4|KIP1|MEN1B|MEN4|P27KIP1 HGNC:1785|MIM:600778|Ensembl:ENSG00000111276|HPRD:02867|Vega:OTTHUMG00000149914 12 12p13.1-p12 cyclin-dependent kinase inhibitor 1B (p27, Kip1) protein-coding cyclin-dependent kinase inhibitor 1B (p27, Kip1) cyclin-dependent kinase i MiR-221 and -222 target the 3'-UTR of Kit and p27(kip1) mRNAs, but interfere with TRAIL signaling mainly through p27(kip1). High expression levels of miR-221 and -222 are needed to maintain the TRAIL-resistant phenotype. 1440 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA CDKN1B apoptosis up Homo sapiens bladder cancer cell 19767219 9606 1027 CDKN4|KIP1|MEN1B|MEN4|P27KIP1 HGNC:1785|MIM:600778|Ensembl:ENSG00000111276|HPRD:02867|Vega:OTTHUMG00000149914 12 12p13.1-p12 cyclin-dependent kinase inhibitor 1B (p27, Kip1) protein-coding cyclin-dependent kinase inhibitor 1B (p27, Kip1) Human miRNA-221 was significantly up-regulated in bladder cancer T24 cells and RT4 cells compared to human normal urothelial cells. T24 cell was TRAIL-resistant cell line. MiRNA-221 silencing predisposed T24 cells to undergo apoptosis induced by TRAIL and resulted in an up-modulation of cyclin-dependent kinase inhibitor p27Kip1. MiRNA-221 suppression promoted the activation of caspase 3 induced by TRAIL in T24 cells. 1441 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA CDKN1B apoptosis Homo sapiens HCC cell 20624000 9606 1027 CDKN4|KIP1|MEN1B|MEN4|P27KIP1 HGNC:1785|MIM:600778|Ensembl:ENSG00000111276|HPRD:02867|Vega:OTTHUMG00000149914 12 12p13.1-p12 cyclin-dependent kinase inhibitor 1B (p27, Kip1) protein-coding cyclin-dependent kinase inhibitor 1B (p27, Kip1) We observed that the microRNAs miR-221/222 are associated with apoptosis regulation under ER stress in human hepatocellular carcinoma (HCC) cells. In these cells, ER stress-induced apoptosis is enhanced by miR-221/222 mimics and attenuated by miR-221/222 inhibitors. miR-221/222 promoted-apoptosis under ER stress is associated with p27(Kip1)- and MEK/ERK-mediated cell cycle regulation. 1442 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA CDKN1B apoptosis up Homo sapiens dendritic cells 21355095 9606 1027 CDKN4|KIP1|MEN1B|MEN4|P27KIP1 HGNC:1785|MIM:600778|Ensembl:ENSG00000111276|HPRD:02867|Vega:OTTHUMG00000149914 12 12p13.1-p12 cyclin-dependent kinase inhibitor 1B (p27, Kip1) protein-coding cyclin-dependent kinase inhibitor 1B (p27, Kip1) Among them, decreased miR-221 and increased miR-155 expression correlated with p27(kip1) accumulation in DCs. Silencing of miR-221 or overexpressing of miR-155 in DCs resulted in p27(kip1) protein increase and DC apoptosis. 1443 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA CDKN1B apoptosis Homo sapiens hepatocarcinoma cell 21586237 9606 1027 CDKN4|KIP1|MEN1B|MEN4|P27KIP1 HGNC:1785|MIM:600778|Ensembl:ENSG00000111276|HPRD:02867|Vega:OTTHUMG00000149914 12 12p13.1-p12 cyclin-dependent kinase inhibitor 1B (p27, Kip1) protein-coding cyclin-dependent kinase inhibitor 1B (p27, Kip1) MiR-221/222 were downregulated by endoplasmic reticulum stress in human hepatocellular carcinoma cells, which subsequently protected human hepatocellular carcinoma cells against endoplasmic reticulum stress-induced apoptosis through p27Kip1 regulation. 1444 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA CDKN1C apoptosis down Homo sapiens colorectal carcinoma cells 21278784 9606 1028 BWCR|BWS|KIP2|WBS|p57|p57Kip2 HGNC:1786|MIM:600856|Ensembl:ENSG00000129757|HPRD:02913|Vega:OTTHUMG00000010040 11 11p15.5 cyclin-dependent kinase inhibitor 1C (p57, Kip2) protein-coding cyclin-dependent kinase inhibitor 1C (p57, Kip2) cyclin-dependent kinase i MiR-221 binds to the target site in the 3'-UTR of the CDKN1C/p57 mRNA to inhibit CDKN1C/p57 expression by post-transcriptional gene silencing to promote CRC occurrence and progress. 1445 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA CDKN1C apoptosis down Homo sapiens colorectal carcinoma cells 21538272 9606 1028 BWCR|BWS|KIP2|WBS|p57|p57Kip2 HGNC:1786|MIM:600856|Ensembl:ENSG00000129757|HPRD:02913|Vega:OTTHUMG00000010040 11 11p15.5 cyclin-dependent kinase inhibitor 1C (p57, Kip2) protein-coding cyclin-dependent kinase inhibitor 1C (p57, Kip2) cyclin-dependent kinase i MiR-221-specific inhibitor significantly enhanced CDKN1C/P57 protein expression, inhibited proliferation of CRC cells and induced apoptosis of CRC cells(P<0.01). 1446 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA DIRAS3 apoptosis Homo sapiens prostate cancer cell 21071579 9606 9077 ARHI|NOEY2 HGNC:687|MIM:605193|Ensembl:ENSG00000162595|HPRD:05547|Vega:OTTHUMG00000009544 1 1p31 DIRAS family, GTP-binding RAS-like 3 protein-coding DIRAS family, GTP-binding RAS-like 3 Overexpression of ARHI inhibited cell proliferation, colony formation, invasion, and induced apoptosis. Further studies on a new mechanism of ARHI downregulation showed a significant inverse relationship between ARHI and miR-221 and 222, which were upregulated in prostate cancer cell lines. 1447 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA DIRAS3 apoptosis down Homo sapiens breast cancer cell 23801152 9606 9077 ARHI|NOEY2 HGNC:687|MIM:605193|Ensembl:ENSG00000162595|HPRD:05547|Vega:OTTHUMG00000009544 1 1p31 DIRAS family, GTP-binding RAS-like 3 protein-coding DIRAS family, GTP-binding RAS-like 3 The overexpression of ARHI could inhibit breast cancer cell proliferation and invasion and induce cell apoptosis. This study demonstrated for the first time that the downregulation of ARHI in breast cancer cells could be regulated by miR-221. 1448 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA KIT apoptosis down Homo sapiens lung cancer cells 18246122 9606 3815 C-Kit|CD117|PBT|SCFR HGNC:6342|MIM:164920|Ensembl:ENSG00000157404|HPRD:01287|Vega:OTTHUMG00000128713 4 4q12 v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog protein-coding v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog cyclin-dependent kinase i MiR-221 and -222 target the 3'-UTR of Kit and p27(kip1) mRNAs, but interfere with TRAIL signaling mainly through p27(kip1). High expression levels of miR-221 and -222 are needed to maintain the TRAIL-resistant phenotype. 1449 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA MAP2K7 apoptosis Homo sapiens HCC cell 20624000 9606 5609 JNKK2|MAPKK7|MEK|MEK 7|MKK7|PRKMK7|SAPKK-4|SAPKK4 HGNC:6847|MIM:603014|Ensembl:ENSG00000076984|Vega:OTTHUMG00000137368 19 19p13.3-p13.2 mitogen-activated protein kinase kinase 7 protein-coding mitogen-activated protein kinase kinase 7 We observed that the microRNAs miR-221/222 are associated with apoptosis regulation under ER stress in human hepatocellular carcinoma (HCC) cells. In these cells, ER stress-induced apoptosis is enhanced by miR-221/222 mimics and attenuated by miR-221/222 inhibitors. miR-221/222 promoted-apoptosis under ER stress is associated with p27(Kip1)- and MEK/ERK-mediated cell cycle regulation. 1450 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA MAPK1 apoptosis Homo sapiens HCC cell 20624000 9606 5594 ERK|ERK-2|ERK2|ERT1|MAPK2|P42MAPK|PRKM1|PRKM2|p38|p40|p41|p41mapk|p42-MAPK HGNC:6871|MIM:176948|Ensembl:ENSG00000100030|HPRD:01496|Vega:OTTHUMG00000030508 22 22q11.21 mitogen-activated protein kinase 1 protein-coding mitogen-activated protein kinase 1 We observed that the microRNAs miR-221/222 are associated with apoptosis regulation under ER stress in human hepatocellular carcinoma (HCC) cells. In these cells, ER stress-induced apoptosis is enhanced by miR-221/222 mimics and attenuated by miR-221/222 inhibitors. miR-221/222 promoted-apoptosis under ER stress is associated with p27(Kip1)- and MEK/ERK-mediated cell cycle regulation. 1451 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA NAIP apoptosis down Homo sapiens neural cell 18759060 9606 4671 BIRC1|NLRB1|psiNAIP HGNC:7634|MIM:600355|Ensembl:ENSG00000249437|Vega:OTTHUMG00000163318 5 5q13.2 NLR family, apoptosis inhibitory protein protein-coding NLR family, apoptosis inhibitory protein We observed selective up-regulation of miRNA-221 and down-regulation of a miRNA-221 messenger RNA target encoding the survivin-1 homolog BIRC1, a neuronal inhibitor of apoptosis protein (NIAP) and marker for neurodegeneration. 1452 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA PTEN apoptosis up Homo sapiens 21481725 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog We identified the PTEN gene as a target of miRNA-221/-222. Furthermore, we found that knocking down miRNA-221/-222 by antisense oligonucleotides upregulated PTEN expression. Upregulated PTEN expression suppressed AKT activity and increased radiation-induced apoptosis, resulting in enhancement of radiosensitivity in tumor cells. 1453 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA PTEN apoptosis down Homo sapiens osteosarcoma cells 23372675 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog The effects of miR-221 were then assessed by cell viability, cell cycle analysis, apoptosis assay, and cisplatin resistance assay. In both cells, upregulation of miR-221 induced cell survival and cisplatin resistance and reduced cell apoptosis. In addition, knockdown of miR-221 inhibited cell growth and cisplatin resistance and induced cell apoptosis. Potential target genes of miR-221 were predicted using bioinformatics. Moreover, luciferase reporter assay and western blot confirmed that PTEN was a direct target of miR-221. 1454 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA PTEN apoptosis down Homo sapiens breast cancers cell 24286315 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog Here, we found that the oncogenic miRNA, miR-221, inhibited apoptosis, induced trastuzumab resistance and promoted metastasis of HER2-positive breast cancers. The tumor suppressor PTEN was identified as a miR-221 target; overexpression of PTEN abrogated the aforementioned miR-221-induced malignant phenotypes of the cells. 1455 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA SNAI1 apoptosis Homo sapiens breast cancer cell 23637992 9606 6615 SLUGH2|SNA|SNAH|SNAIL|SNAIL1|dJ710H13.1 HGNC:11128|MIM:604238|Ensembl:ENSG00000124216|HPRD:05025|Vega:OTTHUMG00000033048 20 20q13.2 snail family zinc finger 1 protein-coding snail family zinc finger 1 MiR-221 knockdown not only blocked cell cycle progression, induced cell apoptosis, and inhibited cell proliferation in-vitro but it also inhibited in-vivo tumor growth by targeting p27(kip1). Furthermore, miR-221 knockdown inhibited cell migration and invasion by altering E-cadherin expression, and its regulatory transcription factors Snail and Slug in human TNBC cell lines. Therefore, miR-221 functions as an oncogene and is essential in regulating tumorigenesis in TNBCs both in vitro as well as in vivo. 1456 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA SNAI2 apoptosis Homo sapiens breast cancer cell 23637992 9606 6591 SLUG|SLUGH1|SNAIL2|WS2D HGNC:11094|MIM:602150|Ensembl:ENSG00000019549|HPRD:03689|Vega:OTTHUMG00000149912 8 8q11 snail family zinc finger 2 protein-coding snail family zinc finger 2 MiR-221 knockdown not only blocked cell cycle progression, induced cell apoptosis, and inhibited cell proliferation in-vitro but it also inhibited in-vivo tumor growth by targeting p27(kip1). Furthermore, miR-221 knockdown inhibited cell migration and invasion by altering E-cadherin expression, and its regulatory transcription factors Snail and Slug in human TNBC cell lines. Therefore, miR-221 functions as an oncogene and is essential in regulating tumorigenesis in TNBCs both in vitro as well as in vivo. 1457 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA TIMP2 apoptosis down Homo sapiens glioma cell 25731730 9606 7077 CSC-21K|DDC8 HGNC:11821|MIM:188825|Ensembl:ENSG00000035862|HPRD:01784|Vega:OTTHUMG00000154517 17 17q25 TIMP metallopeptidase inhibitor 2 protein-coding TIMP metallopeptidase inhibitor 2 Both gain- and loss-of-function studies showed that miR-221/222 regulate cell proliferation, the cell cycle and apoptosis, in addition to, invasion, metastasis, and angiogenesis in glioma cell lines. Subsequent investigations revealed that TIMP2 is a direct target of miR-221/222, and overexpression of TIMP2 reduced the miR-221/222-mediated invasion, metastasis, and angiogenesis of glioma cells. Taken together, our results suggest that the suppression of miR-221/222 may be a feasible approach for inhibiting the malignant behaviors of glioma. 1458 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA TNFSF10 apoptosis Homo sapiens bladder cancer cell 19767219 9606 8743 APO2L|Apo-2L|CD253|TL2|TRAIL HGNC:11925|MIM:603598|Ensembl:ENSG00000121858|HPRD:04670|Vega:OTTHUMG00000156917 3 3q26 tumor necrosis factor (ligand) superfamily, member 10 protein-coding tumor necrosis factor (ligand) superfamily, member 10 Human miRNA-221 was significantly up-regulated in bladder cancer T24 cells and RT4 cells compared to human normal urothelial cells. T24 cell was TRAIL-resistant cell line. MiRNA-221 silencing predisposed T24 cells to undergo apoptosis induced by TRAIL and resulted in an up-modulation of cyclin-dependent kinase inhibitor p27Kip1. MiRNA-221 suppression promoted the activation of caspase 3 induced by TRAIL in T24 cells. 1459 miR-221 hsa-miR-221-5p,hsa-miR-221-3p MIMAT0004568,MIMAT0000278 miRNA apoptosis Homo sapiens pancreatic cancer cells 19730150 9606 1027 CDKN4|KIP1|MEN1B|MEN4|P27KIP1 HGNC:1785|MIM:600778|Ensembl:ENSG00000111276|HPRD:02867|Vega:OTTHUMG00000149914|M2D:hsa-miR-221 12 12p13.1-p12 cyclin-dependent kinase inhibitor 1B (p27, Kip1) protein coding cyclin-dependent kinase inhibitor 1B (p27, Kip1) cyclin-dependent kinase i Antisense inhibition of microRNA-21 or -221 arrests cell cycle, induces apoptosis, and sensitizes the effects of gemcitabine in pancreatic adenocarcinoma. 1460 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA apoptosis Homo sapiens epithelial cancer cell 21042732 9606 MiR-221 and miR-222 (miR-221/222) are frequently up-regulated in human epithelial cancers. However, the mechanism of miR-221/222 action involved in carcinogenesis has not been extensively studied. Here, we found that reduction of miR-221/222 inhibited cell proliferation and induced mitochondrial-mediated apoptosis in human epithelial cancer cells (A549 lung cancer and MCF-7 breast cancer cells). Bioinformatics and luciferase reporter assays showed that miR-221/222 co-modulated the p53 upregulated modulator of apoptosis (PUMA) expression by directly targeting the binding site within the 3'UTR. Together, these findings suggest that PUMA is a direct target of miR-221/222 that functions as an endogenous apoptosis regulator in these epithelial cancers. 1461 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA apoptosis Homo sapiens colorectal carcinoma cell 21515467 9606 The miR-221-specific inhibitor, anti-miR-221, significantly inhibited the expression of miR-221 in Caco2 cells and suppressed the cell proliferation, causing also obvious cell apoptosis (P<0.01). 1462 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA apoptosis Homo sapiens glioma cells 22681957 9606 7078 SFD|K222|K222TA2|HSMRK222 HGNC:11822|ENSG00000100234|HPRD:01785|MIM:188826|Vega:OTTHUMG00000030784 22 22q12.3 TIMP metallopeptidase inhibitor 3 protein coding TIMP metallopeptidase inhibitor 3 MiR-221 and miR-222 (miR-221/222), upregulated in gliomas, can regulate glioma cell cycle progression and apoptosis, respectively. 1463 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA apoptosis Homo sapiens hepatocellular carcinoma cell 23320393 9606 Functionally, cell growth was inhibited, cell cycle was arrested in G1/S-phase and apoptosis was increased by miR-221 inhibitor in vitro. Likewise, miR-221 mimic accelerated the cell growth. 1464 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA apoptosis Homo sapiens glioblastoma cell 24780067 9606 In the present study, we explored the effects of miRNA-221 on BCNU-resistant glioma cells and the possible molecular mechanisms by which miRNA-221 mediated the cell proliferation, survival, apoptosis and BCNU resistance were investigated. 1465 miR-221 hsa-miR-221-3p,hsa-miR-221-5p MIMAT0000278,MIMAT0004568 miRNA apoptosis Homo sapiens lung cancer cell 25641933 9606 Cell cycle and apoptosis analyses revealed that growth suppression by miR-221 and miR-222 occurred through intra-S-phase arrest and/or apoptosis. Finally, lung cancer cell lines transfected with miR-221 or miR-222 became more sensitive to the S-phase targeting drugs, possibly due to an increased S-phase population. In conclusion, our data are the first to show tumor-suppressive effects of miR-221 and miR-222 on lung cancer, warranting testing their potential as therapeutics for the disease. 1466 miR-222 hsa-miR-222-3p,hsa-miR-222-5p MIMAT0000279,MIMAT0004569 miRNA ADAM17 apoptosis down Homo sapiens colorectal carcinoma cells 22677042 9606 6868 ADAM18|CD156B|CSVP|NISBD|TACE HGNC:195|MIM:603639|Ensembl:ENSG00000151694|HPRD:04703|Vega:OTTHUMG00000090425 2 2p25 ADAM metallopeptidase domain 17 protein-coding ADAM metallopeptidase domain 17 We found that elevated levels of miR-222 in the mimics-transfected HCT116/L-OHP and HCT-8/VCR cells reduced the ADAM-17 protein level and the luciferase activity of an ADAM-17 3' untranslated region-based reporter and sensitized these cells' apoptosis to some anticancer drugs. 1467 miR-222 hsa-miR-222-3p,hsa-miR-222-5p MIMAT0000279,MIMAT0004569 miRNA AKT1 apoptosis Homo sapiens hepatocellular carcinoma cell 25096647 9606 207 AKT|CWS6|PKB|PKB-ALPHA|PRKBA|RAC|RAC-ALPHA HGNC:391|MIM:164730|Ensembl:ENSG00000142208|HPRD:01261|Vega:OTTHUMG00000170795 14 14q32.32 v-akt murine thymoma viral oncogene homolog 1 protein-coding v-akt murine thymoma viral oncogene homolog 1 Importantly, our study also showed that miR-222 could regulate the expression of phosphorylation PI3K and AKT, which might contribute to miR-222 conferred SOR resistance in HepG2 cells. In conclusion, this study demonstrates that miR-222 can promote cell proliferation, migration and invasion, and decrease cell apoptosis, as well as enhance the resistance of HCC cells to sorafenib miR-222 through activating the PI3K/AKT signaling pathway. 1468 miR-222 hsa-miR-222-5p,hsa-miR-222-3p MIMAT0004569,MIMAT0000279 miRNA BBC3 apoptosis down Homo sapiens glioblastoma cells 20813046 9606 27113 JFY-1|JFY1|PUMA HGNC:17868|MIM:605854|Ensembl:ENSG00000105327|HPRD:16165|Vega:OTTHUMG00000183489 19 19q13.3-q13.4 BCL2 binding component 3 protein-coding BCL2 binding component 3 bcl-2-binding component 3 Here we showed that miR-221/222 inhibited cell apoptosis by targeting pro-apoptotic gene PUMA in human glioma cells. Enforced expression of miR-22/222 induced cell survival whereas knockdown of miR-221/222 rendered cells to apoptosis. 1469 miR-222 hsa-miR-222-5p,hsa-miR-222-3p MIMAT0004569,MIMAT0000279 miRNA BBC3 apoptosis Homo sapiens epithelial cancer cell 21042732 9606 27113 JFY-1|JFY1|PUMA HGNC:17868|MIM:605854|Ensembl:ENSG00000105327|HPRD:16165|Vega:OTTHUMG00000183489 19 19q13.3-q13.4 BCL2 binding component 3 protein-coding BCL2 binding component 3 Bioinformatics and luciferase reporter assays showed that miR-221/222 co-modulated the p53 upregulated modulator of apoptosis (PUMA) expression by directly targeting the binding site within the 3'UTR. Together, these findings suggest that PUMA is a direct target of miR-221/222 that functions as an endogenous apoptosis regulator in these epithelial cancers. 1470 miR-222 hsa-miR-222-3p,hsa-miR-222-5p MIMAT0000279,MIMAT0004569 miRNA BBC3 apoptosis down Homo sapiens oral squamous cell 24452416 9606 27113 JFY-1|JFY1|PUMA HGNC:17868|MIM:605854|Ensembl:ENSG00000105327|HPRD:16165|Vega:OTTHUMG00000183489 19 19q13.3-q13.4 BCL2 binding component 3 protein-coding BCL2 binding component 3 In the Pre-miR-222 transfection group showed increased expression of miR-222 and decreased expression of PUMA, enhanced proliferation and invasion abilities, and decreased apoptosis. 1471 miR-222 hsa-miR-222-3p,hsa-miR-222-5p MIMAT0000279,MIMAT0004569 miRNA BBC3 apoptosis up Homo sapiens oral squamous cell 25474084 9606 27113 JFY-1|JFY1|PUMA HGNC:17868|MIM:605854|Ensembl:ENSG00000105327|HPRD:16165|Vega:OTTHUMG00000183489 19 19q13.3-q13.4 BCL2 binding component 3 protein-coding BCL2 binding component 3 The present study explored the role and mechanism of miR-222 in increasing the expression of p53 up-regulated modulator of apoptosis (PUMA) and enhancing the sensitivity of OSCC to cisplatin (CDDP) 1472 miR-222 hsa-miR-222-5p,hsa-miR-222-3p MIMAT0004569,MIMAT0000279 miRNA CDKN1B apoptosis down Homo sapiens lung cancer cells 18246122 9606 1027 CDKN4|KIP1|MEN1B|MEN4|P27KIP1 HGNC:1785|MIM:600778|Ensembl:ENSG00000111276|HPRD:02867|Vega:OTTHUMG00000149914 12 12p13.1-p12 cyclin-dependent kinase inhibitor 1B (p27, Kip1) protein-coding cyclin-dependent kinase inhibitor 1B (p27, Kip1) cyclin-dependent kinase i MiR-221 and -222 target the 3'-UTR of Kit and p27(kip1) mRNAs, but interfere with TRAIL signaling mainly through p27(kip1).High expression levels of miR-221 and -222 are needed to maintain the TRAIL-resistant phenotype. 1473 miR-222 hsa-miR-222-5p,hsa-miR-222-3p MIMAT0004569,MIMAT0000279 miRNA CDKN1B apoptosis Homo sapiens HCC cell 20624000 9606 1027 CDKN4|KIP1|MEN1B|MEN4|P27KIP1 HGNC:1785|MIM:600778|Ensembl:ENSG00000111276|HPRD:02867|Vega:OTTHUMG00000149914 12 12p13.1-p12 cyclin-dependent kinase inhibitor 1B (p27, Kip1) protein-coding cyclin-dependent kinase inhibitor 1B (p27, Kip1) Cancer cells are relatively resistant to endoplasmic reticulum (ER) stress-induced apoptosis. However, the underlying mechanisms remain largely unclear. We observed that the microRNAs miR-221/222 are associated with apoptosis regulation under ER stress in human hepatocellular carcinoma (HCC) cells. Induction of ER stress does not trigger significant apoptosis but obviously causes downregulation of miR-221/222 in HCC cells. In these cells, ER stress-induced apoptosis is enhanced by miR-221/222 mimics and attenuated by miR-221/222 inhibitors. miR-221/222 promoted-apoptosis under ER stress is associated with p27(Kip1)- and MEK/ERK-mediated cell cycle regulation. Our results suggest that suppression of miR-221/222 plays a crucial role in the protection against apoptosis induced by ER stress in HCC cells. 1474 miR-222 hsa-miR-222-5p,hsa-miR-222-3p MIMAT0004569,MIMAT0000279 miRNA CDKN1B apoptosis Homo sapiens hepatocarcinoma cell 21586237 9606 1027 CDKN4|KIP1|MEN1B|MEN4|P27KIP1 HGNC:1785|MIM:600778|Ensembl:ENSG00000111276|HPRD:02867|Vega:OTTHUMG00000149914 12 12p13.1-p12 cyclin-dependent kinase inhibitor 1B (p27, Kip1) protein-coding cyclin-dependent kinase inhibitor 1B (p27, Kip1) MiR-221/222 were downregulated by endoplasmic reticulum stress in human hepatocellular carcinoma cells, which subsequently protected human hepatocellular carcinoma cells against endoplasmic reticulum stress-induced apoptosis through p27Kip1 regulation. 1475 miR-222 hsa-miR-222-5p,hsa-miR-222-3p MIMAT0004569,MIMAT0000279 miRNA DIRAS3 apoptosis Homo sapiens prostate cancer cell 21071579 9606 9077 ARHI|NOEY2 HGNC:687|MIM:605193|Ensembl:ENSG00000162595|HPRD:05547|Vega:OTTHUMG00000009544 1 1p31 DIRAS family, GTP-binding RAS-like 3 protein-coding DIRAS family, GTP-binding RAS-like 3 Overexpression of ARHI inhibited cell proliferation, colony formation, invasion, and induced apoptosis. Further studies on a new mechanism of ARHI downregulation showed a significant inverse relationship between ARHI and miR-221 and 222, which were upregulated in prostate cancer cell lines. 1476 miR-222 hsa-miR-222-3p,hsa-miR-222-5p MIMAT0000279,MIMAT0004569 miRNA DKK2 apoptosis down Homo sapiens glioma cell 23587485 9606 27123 DKK-2 HGNC:2892|MIM:605415|Ensembl:ENSG00000155011|HPRD:05658|Vega:OTTHUMG00000131216 4 4q25 dickkopf WNT signaling pathway inhibitor 2 protein-coding dickkopf WNT signaling pathway inhibitor 2 MiR-222 in glioma can regulate cell cycle progression and apoptosis. However, the relationship between miR-222 and Wnt/¦Â-catenin signaling pathway in glioma remains unknown. Here, we found that the Dickkopf-2 gene (DKK2) was a direct target of miR-222 by target prediction analysis and dual luciferase reporter assay. 1477 miR-222 hsa-miR-222-5p,hsa-miR-222-3p MIMAT0004569,MIMAT0000279 miRNA KIT apoptosis down Homo sapiens lung cancer cells 18246122 9606 3815 C-Kit|CD117|PBT|SCFR HGNC:6342|MIM:164920|Ensembl:ENSG00000157404|HPRD:01287|Vega:OTTHUMG00000128713 4 4q12 v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog protein-coding v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog cyclin-dependent kinase i MiR-221 and -222 target the 3'-UTR of Kit and p27(kip1) mRNAs, but interfere with TRAIL signaling mainly through p27(kip1).High expression levels of miR-221 and -222 are needed to maintain the TRAIL-resistant phenotype. 1478 miR-222 hsa-miR-222-5p,hsa-miR-222-3p MIMAT0004569,MIMAT0000279 miRNA MAP2K7 apoptosis Homo sapiens HCC cell 20624000 9606 5609 JNKK2|MAPKK7|MEK|MEK 7|MKK7|PRKMK7|SAPKK-4|SAPKK4 HGNC:6847|MIM:603014|Ensembl:ENSG00000076984|Vega:OTTHUMG00000137368 19 19p13.3-p13.2 mitogen-activated protein kinase kinase 7 protein-coding mitogen-activated protein kinase kinase 7 Cancer cells are relatively resistant to endoplasmic reticulum (ER) stress-induced apoptosis. However, the underlying mechanisms remain largely unclear. We observed that the microRNAs miR-221/222 are associated with apoptosis regulation under ER stress in human hepatocellular carcinoma (HCC) cells. Induction of ER stress does not trigger significant apoptosis but obviously causes downregulation of miR-221/222 in HCC cells. In these cells, ER stress-induced apoptosis is enhanced by miR-221/222 mimics and attenuated by miR-221/222 inhibitors. miR-221/222 promoted-apoptosis under ER stress is associated with p27(Kip1)- and MEK/ERK-mediated cell cycle regulation. Our results suggest that suppression of miR-221/222 plays a crucial role in the protection against apoptosis induced by ER stress in HCC cells. 1479 miR-222 hsa-miR-222-5p,hsa-miR-222-3p MIMAT0004569,MIMAT0000279 miRNA MAPK1 apoptosis Homo sapiens HCC cell 20624000 9606 5594 ERK|ERK-2|ERK2|ERT1|MAPK2|P42MAPK|PRKM1|PRKM2|p38|p40|p41|p41mapk|p42-MAPK HGNC:6871|MIM:176948|Ensembl:ENSG00000100030|HPRD:01496|Vega:OTTHUMG00000030508 22 22q11.21 mitogen-activated protein kinase 1 protein-coding mitogen-activated protein kinase 1 Cancer cells are relatively resistant to endoplasmic reticulum (ER) stress-induced apoptosis. However, the underlying mechanisms remain largely unclear. We observed that the microRNAs miR-221/222 are associated with apoptosis regulation under ER stress in human hepatocellular carcinoma (HCC) cells. Induction of ER stress does not trigger significant apoptosis but obviously causes downregulation of miR-221/222 in HCC cells. In these cells, ER stress-induced apoptosis is enhanced by miR-221/222 mimics and attenuated by miR-221/222 inhibitors. miR-221/222 promoted-apoptosis under ER stress is associated with p27(Kip1)- and MEK/ERK-mediated cell cycle regulation. Our results suggest that suppression of miR-221/222 plays a crucial role in the protection against apoptosis induced by ER stress in HCC cells. 1480 miR-222 hsa-miR-222-3p,hsa-miR-222-5p MIMAT0000279,MIMAT0004569 miRNA PIK3CA apoptosis Homo sapiens hepatocellular carcinoma cell 25096647 9606 5290 CLOVE|CWS5|MCAP|MCM|MCMTC|PI3K|p110-alpha HGNC:8975|MIM:171834|HPRD:01382 3 3q26.3 phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha protein-coding phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha Importantly, our study also showed that miR-222 could regulate the expression of phosphorylation PI3K and AKT, which might contribute to miR-222 conferred SOR resistance in HepG2 cells. In conclusion, this study demonstrates that miR-222 can promote cell proliferation, migration and invasion, and decrease cell apoptosis, as well as enhance the resistance of HCC cells to sorafenib miR-222 through activating the PI3K/AKT signaling pathway. 1481 miR-222 hsa-miR-222-3p,hsa-miR-222-5p MIMAT0000279,MIMAT0004569 miRNA PTEN apoptosis up Homo sapiens 21481725 9606 5728 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|TEP1 HGNC:9588|MIM:601728|HPRD:03431 10 10q23.3 phosphatase and tensin homolog protein-coding phosphatase and tensin homolog We identified the PTEN gene as a target of miRNA-221/-222. Furthermore, we found that knocking down miRNA-221/-222 by antisense oligonucleotides upregulated PTEN expression. Upregulated PTEN expression suppressed AKT activity and increased radiation-induced apoptosis, resulting in enhancement of radiosensitivity in tumor cells. 1482 miR-222 hsa-miR-222-3p,hsa-miR-222-5p MIMAT0000279,MIMAT0004569 miRNA TIMP2 apoptosis down Homo sapiens glioma cell 25731730 9606 7077 CSC-21K|DDC8 HGNC:11821|MIM:188825|Ensembl:ENSG00000035862|HPRD:01784|Vega:OTTHUMG00000154517 17 17q25 TIMP metallopeptidase inhibitor 2 protein-coding TIMP metallopeptidase inhibitor 2 Both gain- and loss-of-function studies showed that miR-221/222 regulate cell proliferation, the cell cycle and apoptosis, in addition to, invasion, metastasis, and angiogenesis in glioma cell lines. Subsequent investigations revealed that TIMP2 is a direct target of miR-221/222, and overexpression of TIMP2 reduced the miR-221/222-mediated invasion, metastasis, and angiogenesis of glioma cells. Taken together, our results suggest that the suppression of miR-221/222 may be a feasible approach for inhibiting the malignant behaviors of glioma. 1483 miR-222 hsa-miR-222-3p,hsa-miR-222-5p MIMAT0000279,MIMAT0004569 miRNA apoptosis Homo sapiens epithelial cancer cell 21042732 9606 MiR-221 and miR-222 (miR-221/222) are frequently up-regulated in human epithelial cancers. However, the mechanism of miR-221/222 action involved in carcinogenesis has not been extensively studied. Here, we found that reduction of miR-221/222 inhibited cell proliferation and induced mitochondrial-mediated apoptosis in human epithelial cancer cells (A549 lung cancer and MCF-7 breast cancer cells). Bioinformatics and luciferase reporter assays showed that miR-221/222 co-modulated the p53 upregulated modulator of apoptosis (PUMA) expression by directly targeting the binding site within the 3'UTR. Together, these findings suggest that PUMA is a direct target of miR-221/222 that functions as an endogenous apoptosis regulator in these epithelial cancers. 1484 miR-222 hsa-miR-222-3p,hsa-miR-222-5p, MIMAT0000279,MIMAT0004569 miRNA apoptosis Homo sapiens glioma cells 22681957 9606 7078 SFD|K222|K222TA2|HSMRK222 HGNC:11822|ENSG00000100234|HPRD:01785|MIM:188826|Vega:OTTHUMG00000030784 22 22q12.3 TIMP metallopeptidase inhibitor 3 protein coding TIMP metallopeptidase inhibitor 3 MiR-221 and miR-222 (miR-221/222), upregulated in gliomas, can regulate glioma cell cycle progression and apoptosis, respectively. 1485 miR-222 hsa-miR-222-3p,hsa-miR-222-5p MIMAT0000279,MIMAT0004569 miRNA apoptosis Homo sapiens leukemic cells 23522449 9606 In our in vitro studies miR-222 significantly inhibited proliferation, and caused cell cycle arrest and apoptosis in leukemic cells. 1486 miR-222 hsa-miR-222-3p,hsa-miR-222-5p MIMAT0000279,MIMAT0004569 miRNA apoptosis Homo sapiens lung cancer cell 25641933 9606 Cell cycle and apoptosis analyses revealed that growth suppression by miR-221 and miR-222 occurred through intra-S-phase arrest and/or apoptosis. Finally, lung cancer cell lines transfected with miR-221 or miR-222 became more sensitive to the S-phase targeting drugs, possibly due to an increased S-phase population. In conclusion, our data are the first to show tumor-suppressive effects of miR-221 and miR-222 on lung cancer, warranting testing their potential as therapeutics for the disease. 1487 miR-223 hsa-miR-223-3p,hsa-miR-223-5p MIMAT0004570,MIMAT0000280 miRNA AKT1 apoptosis down Homo sapiens osteosarcoma cell 23208072 9606 207 AKT|CWS6|PKB|PKB-ALPHA|PRKBA|RAC|RAC-ALPHA HGNC:391|MIM:164730|Ensembl:ENSG00000142208|HPRD:01261|Vega:OTTHUMG00000170795 14 14q32.32 v-akt murine thymoma viral oncogene homolog 1 protein-coding v-akt murine thymoma viral oncogene homolog 1 Furthermore, overexpression of miR-223 results in significant inhibition of cell growth on culture plates. Moreover, cancer cells showed significant G0/G1 arrest and increased apoptosis due to gene silencing. Protein levels of PI3k, p-Akt, mTOR, and Bcl-2 were decreased, whereas Bid levels were increased. Microvessel density as assessed by CD34 levels and cell growth by PCNA levels decreased according to immunohistochemical analysis. 1488 miR-223 hsa-miR-223-3p,hsa-miR-223-5p MIMAT0004570,MIMAT0000280 miRNA BCL2 apoptosis down Homo sapiens osteosarcoma cell 23208072 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 Furthermore, overexpression of miR-223 results in significant inhibition of cell growth on culture plates. Moreover, cancer cells showed significant G0/G1 arrest and increased apoptosis due to gene silencing. Protein levels of PI3k, p-Akt, mTOR, and Bcl-2 were decreased, whereas Bid levels were increased. Microvessel density as assessed by CD34 levels and cell growth by PCNA levels decreased according to immunohistochemical analysis. 1489 miR-223 hsa-miR-223-3p,hsa-miR-223-5p MIMAT0000280,MIMAT0004570 miRNA BID apoptosis up Homo sapiens osteosarcoma cell 23208072 9606 637 FP497 HGNC:1050|MIM:601997|Ensembl:ENSG00000015475|HPRD:03590|Vega:OTTHUMG00000150087 22 22q11.1 BH3 interacting domain death agonist protein-coding BH3 interacting domain death agonist Furthermore, overexpression of miR-223 results in significant inhibition of cell growth on culture plates. Moreover, cancer cells showed significant G0/G1 arrest and increased apoptosis due to gene silencing. Protein levels of PI3k, p-Akt, mTOR, and Bcl-2 were decreased, whereas Bid levels were increased. Microvessel density as assessed by CD34 levels and cell growth by PCNA levels decreased according to immunohistochemical analysis. 1490 miR-223 hsa-miR-223-3p,hsa-miR-223-5p MIMAT0004570,MIMAT0000280 miRNA FBXW7 apoptosis down Homo sapiens Gastric cancer cell 22270966 9606 55294 AGO|CDC4|FBW6|FBW7|FBX30|FBXO30|FBXW6|SEL-10|SEL10|hAgo|hCdc4 HGNC:16712|MIM:606278|Ensembl:ENSG00000109670|HPRD:05888|Vega:OTTHUMG00000185246 4 4q31.3 F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase protein-coding F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase Gastric cancer cell line SGC7901, transfected with miR-223, showed significant reduction in cellular apoptosis and increased proliferation and invasion in vitro. Similar results were found in tumorigenesis assays performed in nude mice. Moreover, 19 of 22 cancer tissue samples highly expressed miR-223, when compared with patient-matched normal gastric mucosa. Specifically, patients with lymph node metastasis or metastatic disease (M1) at an advanced pathological stage showed significantly higher expression of miR-223. FBXW7/hCdc4 protein (FBW7) levels in gastric cancer cases were inversely correlated with miR-223 expression. Overexpression of miR-223 in gastric cancer cell lines decreased FBW7 expression at the translational level and decreased FBXW7/hCdc4-driven luciferase-reporter activity. 1491 miR-223 hsa-miR-223-3p,hsa-miR-223-5p MIMAT0000280,MIMAT0004570 miRNA FBXW7 apoptosis down Homo sapiens gastric cancer cell 25159729 9606 55294 AGO|CDC4|FBW6|FBW7|FBX30|FBXO30|FBXW6|SEL-10|SEL10|hAgo|hCdc4 HGNC:16712|MIM:606278|Ensembl:ENSG00000109670|HPRD:05888|Vega:OTTHUMG00000185246 4 4q31.3 F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase protein-coding F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase Overexpression of miR-223 decreased FBXW7 expression and the sensitivity of GC cells to trastuzumab, while suppression of miR-223 restored FBXW7 expression and the sensitivity of GC cells to trastuzumab. Moreover, overexpression of miR-223 significantly suppressed trastuzumab-induced apoptosis. This study is the first report to reveal that the miR-223/FBXW7 pathway regulates the sensitivity of a HER2-positive GC cell line to trastuzumab through the modulation of apoptosis. 1492 miR-223 hsa-miR-223-3p,hsa-miR-223-5p MIMAT0004570,MIMAT0000280 miRNA IGF1R apoptosis Homo sapiens embryonic stem cell 24250812 9606 3480 CD221|IGFIR|IGFR|JTK13 HGNC:5465|MIM:147370|Ensembl:ENSG00000140443|HPRD:00932|Vega:OTTHUMG00000149851 15 15q26.3 insulin-like growth factor 1 receptor protein-coding insulin-like growth factor 1 receptor Based on the identification of complementary binding sites in miR-223 and IGF-1R mRNA, it is proposed that miR-223 acts as a local regulator of IGF-1R. Therefore, levels of miR-223 were detected in differentiated versus undifferentiated hESCs.In addition, proliferation, apoptosis, and differentiation were assayed in these two hESC populations and were compared in the presence of exogenous miR-223 and miR-223 inhibitor. Inhibition of miR-223 was found to maintain the undifferentiated state of hESCs, while addition of miR-223 induced differentiation. Furthermore, these effects were found to be likely dependent on IGF-1R/Akt signaling. 1493 miR-223 hsa-miR-223-3p,hsa-miR-223-5p MIMAT0004570,MIMAT0000280 miRNA IGF1R apoptosis down Homo sapiens endothelial cell 24307738 9606 3480 CD221|IGFIR|IGFR|JTK13 HGNC:5465|MIM:147370|Ensembl:ENSG00000140443|HPRD:00932|Vega:OTTHUMG00000149851 15 15q26.3 insulin-like growth factor 1 receptor protein-coding insulin-like growth factor 1 receptor Finally, in HUVECs, exogenous platelet miR-223 decreased the level of insulin-like growth factor 1 receptor and thus promoted HUVEC apoptosis induced by advanced glycation end products. 1494 miR-223 hsa-miR-223-3p,hsa-miR-223-5p MIMAT0000280,MIMAT0004570 miRNA MTOR apoptosis down Homo sapiens osteosarcoma cell 23208072 9606 2475 FRAP|FRAP1|FRAP2|RAFT1|RAPT1 HGNC:3942|MIM:601231|Ensembl:ENSG00000198793|HPRD:03134|Vega:OTTHUMG00000002001 1 1p36.2 mechanistic target of rapamycin (serine/threonine kinase) protein-coding mechanistic target of rapamycin (serine/threonine kinase) Furthermore, overexpression of miR-223 results in significant inhibition of cell growth on culture plates. Moreover, cancer cells showed significant G0/G1 arrest and increased apoptosis due to gene silencing. Protein levels of PI3k, p-Akt, mTOR, and Bcl-2 were decreased, whereas Bid levels were increased. Microvessel density as assessed by CD34 levels and cell growth by PCNA levels decreased according to immunohistochemical analysis. 1495 miR-223 hsa-miR-223-3p,hsa-miR-223-5p MIMAT0000280,MIMAT0004570 miRNA PIK3CA apoptosis down Homo sapiens osteosarcoma cell 23208072 9606 5290 CLOVE|CWS5|MCAP|MCM|MCMTC|PI3K|p110-alpha HGNC:8975|MIM:171834|HPRD:01382 3 3q26.3 phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha protein-coding phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha Furthermore, overexpression of miR-223 results in significant inhibition of cell growth on culture plates. Moreover, cancer cells showed significant G0/G1 arrest and increased apoptosis due to gene silencing. Protein levels of PI3k, p-Akt, mTOR, and Bcl-2 were decreased, whereas Bid levels were increased. Microvessel density as assessed by CD34 levels and cell growth by PCNA levels decreased according to immunohistochemical analysis. 1496 miR-223 hsa-miR-223-3p,hsa-miR-223-5p MIMAT0000280,MIMAT0004570 miRNA SLC8A1 apoptosis down Homo sapiens penile?cell 25481039 9606 6546 NCX1 HGNC:11068|MIM:182305|Ensembl:ENSG00000183023|HPRD:01659 2 2p22.1 solute carrier family 8 (sodium/calcium exchanger), member 1 protein-coding solute carrier family 8 (sodium/calcium exchanger), member 1 Down-regulation of the SLC8A1 gene, most likely mediated by its regulator miR-223, can lead to reduced calcium levels in PeCa and, consequently, to suppression of apoptosis and increased tumor cell proliferation. These data suggest that the miR-223-NCX1-calcium-signaling axis may represent a potential therapeutic approach in PeCa. 1497 miR-224 hsa-miR-224-5p,hsa-miR-224-3p MIMAT0000281,MIMAT0009198 miRNA API5 apoptosis Homo sapiens hepatocellular carcinoma cells 18319255 9606 8539 AAC-11|AAC11 HGNC:594|MIM:609774|Ensembl:ENSG00000166181|HPRD:16500|Vega:OTTHUMG00000166395 11 11p11.2 apoptosis inhibitor 5 protein-coding apoptosis inhibitor 5 FIF|antiapoptosis clone 1 Profiling microRNA expression in hepatocellular carcinoma reveals microRNA-224 up-regulation and apoptosis inhibitor-5 as a microRNA-224-specific target. 1498 miR-224 hsa-miR-224-5p,hsa-miR-224-3p MIMAT0000281,MIMAT0009198 miRNA API5 apoptosis down Homo sapiens mesenchymal stem cells 22326282 9606 8539 AAC-11|AAC11 HGNC:594|MIM:609774|Ensembl:ENSG00000166181|HPRD:16500|Vega:OTTHUMG00000166395 11 11p11.2 apoptosis inhibitor 5 protein-coding apoptosis inhibitor 5 We could confirm the already known regulation of the apoptosis inhibitor API5 by miR-224 and could further identify three novel miR-224 target genes (SMAD5, SLMAP, H3.3B). 1499 miR-224 hsa-miR-224-5p,hsa-miR-224-3p MIMAT0000281,MIMAT0009198 miRNA API5 apoptosis up Homo sapiens systemic lupus erythematosus T cells 23199328 9606 8539 AAC-11|AAC11 HGNC:594|MIM:609774|Ensembl:ENSG00000166181|HPRD:16500|Vega:OTTHUMG00000166395 11 11p11.2 apoptosis inhibitor 5 protein-coding apoptosis inhibitor 5 We further found that STAT1 mRNA targeted by miR-145 was over-expressed and apoptosis inhibitory protein 5 (API5) mRNA targeted by miR-224 was under-expressed in SLE T cells. 1500 miR-224 hsa-miR-224-5p,hsa-miR-224-3p MIMAT0000281,MIMAT0009198 miRNA BCL2 apoptosis down Homo sapiens hepatocellular carcinoma cell 22989374 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 The high-ranking genes CDC42, CDH1, PAK2, BCL-2, and MAPK1 were confirmed as important targets of miR-224 and involvement in hepatocarcinogenesis. Overexpression of miR-224 significantly in Hek293 and Huh7 cells altered the expression levels of CDC42, CDH1, PAK2, and BCL-2 at both mRNA and protein levels. 1501 miR-224 hsa-miR-224-5p,hsa-miR-224-3p MIMAT0000281,MIMAT0009198 miRNA BCL2 apoptosis down Homo sapiens gastric cancer cell 24796455 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 Flow cytometry indicated that the apoptotic index was (15.68 ¡À 1.46)% in the miR-224 ASO group and (3.36 ¡À 0.88)% in the control group (P < 0.01). In addition, the expressions of Bcl2 mRNA and protein were 1.05 ¡À 0.04 and 0.21 ¡À 0.03 in the miR-224 ASO group, significantly lower than that in the control group (4.87 ¡À 0.96 and 0.88 ¡À 0.09, P < 0.01). The in vivo study further showed that the tumor volume in the experimental group is significantly smaller than that in the control group (P = 0.01). 1502 miR-224 hsa-miR-224-5p,hsa-miR-224-3p MIMAT0000281,MIMAT0009198 miRNA CDC42 apoptosis down Homo sapiens hepatocellular carcinoma cell 22989374 9606 998 CDC42Hs|G25K HGNC:1736|MIM:116952|Ensembl:ENSG00000070831|HPRD:00309|Vega:OTTHUMG00000002753 1 1p36.1 cell division cycle 42 protein-coding cell division cycle 42 The high-ranking genes CDC42, CDH1, PAK2, BCL-2, and MAPK1 were confirmed as important targets of miR-224 and involvement in hepatocarcinogenesis. Overexpression of miR-224 significantly in Hek293 and Huh7 cells altered the expression levels of CDC42, CDH1, PAK2, and BCL-2 at both mRNA and protein levels. 1503 miR-224 hsa-miR-224-5p,hsa-miR-224-3p MIMAT0000281,MIMAT0009198 miRNA CDH1 apoptosis down Homo sapiens hepatocellular carcinoma cell 22989374 9606 999 Arc-1|CD324|CDHE|ECAD|LCAM|UVO HGNC:1748|MIM:192090|Ensembl:ENSG00000039068|HPRD:01885|Vega:OTTHUMG00000137561 16 16q22.1 cadherin 1, type 1, E-cadherin (epithelial) protein-coding cadherin 1, type 1, E-cadherin (epithelial) The high-ranking genes CDC42, CDH1, PAK2, BCL-2, and MAPK1 were confirmed as important targets of miR-224 and involvement in hepatocarcinogenesis. Overexpression of miR-224 significantly in Hek293 and Huh7 cells altered the expression levels of CDC42, CDH1, PAK2, and BCL-2 at both mRNA and protein levels. 1504 miR-224 hsa-miR-224-5p,hsa-miR-224-3p MIMAT0000281,MIMAT0009198 miRNA CDKN1A apoptosis down Homo sapiens 24921914 9606 1026 CAP20|CDKN1|CIP1|MDA-6|P21|SDI1|WAF1|p21CIP1 HGNC:1784|MIM:116899|Ensembl:ENSG00000124762|HPRD:00298|Vega:OTTHUMG00000014603 6 6p21.2 cyclin-dependent kinase inhibitor 1A (p21, Cip1) protein-coding cyclin-dependent kinase inhibitor 1A (p21, Cip1) MiR-224 promotes the chemoresistance of human lung adenocarcinoma cells to cisplatin via regulating G?/S transition and apoptosis by targeting p21(WAF1/CIP1). 1505 miR-224 hsa-miR-224-5p,hsa-miR-224-3p MIMAT0000281,MIMAT0009198 miRNA PAK2 apoptosis down Homo sapiens hepatocellular carcinoma cell 22989374 9606 5062 PAK65|PAKgamma HGNC:8591|MIM:605022|Ensembl:ENSG00000180370|HPRD:05428|Vega:OTTHUMG00000155534 3 3q29 p21 protein (Cdc42/Rac)-activated kinase 2 protein-coding p21 protein (Cdc42/Rac)-activated kinase 2 The high-ranking genes CDC42, CDH1, PAK2, BCL-2, and MAPK1 were confirmed as important targets of miR-224 and involvement in hepatocarcinogenesis. Overexpression of miR-224 significantly in Hek293 and Huh7 cells altered the expression levels of CDC42, CDH1, PAK2, and BCL-2 at both mRNA and protein levels. 1506 miR-224 hsa-miR-224-5p,hsa-miR-224-3p MIMAT0000281,MIMAT0009198 miRNA TRIB1 apoptosis down Homo sapiens prostate cancer cell 24382668 9606 10221 C8FW|GIG-2|GIG2|SKIP1|TRB-1|TRB1 HGNC:16891|MIM:609461|Ensembl:ENSG00000173334|HPRD:09863|Vega:OTTHUMG00000165007 8 8q24.13 tribbles pseudokinase 1 protein-coding tribbles pseudokinase 1 Forced expression of miR-224 suppressed PCa cell proliferation, invasion and migration, and promoted cell apoptosis by downregulating TRIB1. 1507 miR-224 hsa-miR-224-5p,hsa-miR-224-3p MIMAT0000281,MIMAT0009198 miRNA apoptosis Homo sapiens NSCLC cell 25410592 9606 MiR-224 mimics in NSCLC A549 cells was able to reduce cell proliferation, invasion, and migration, and promote cell apoptosis. 1508 miR-224-5p hsa-miR-224-5p MIMAT0000281 miRNA PRKCD apoptosis Homo sapiens 25017423 9606 5580 CVID9|MAY1|PKCD|nPKC-delta HGNC:9399|MIM:176977|Ensembl:ENSG00000163932|HPRD:01501|Vega:OTTHUMG00000133659 3 3p21.31 protein kinase C, delta protein-coding protein kinase C, delta It is of note that enforced expression of miR-224-5p enhanced chemoresistance to cisplatin in ovarian cancer cells through apoptosis reversion. We predicted and identified the PRKCD gene as one of the targets of miR-224-5p in mediating the primary chemoresistance of ovarian cancer patients. We showed reciprocal expression of miR-224-5p and PRKCD by quantitative analysis in complete response and incomplete response patients in?vivo, and 2 pairs of cisplatin resistance and sensitive cell lines in?vitro, after either miR-224-5p overexpression or knockdown transfection. 1509 miR-23a hsa-miR-23a-3p,hsa-miR-23a-5p MIMAT0000078,MIMAT0004496 miRNA CASP3 apoptosis down Homo sapiens varian granulosa cells 22653319 9606 836 CPP32|CPP32B|SCA-1 HGNC:1504|MIM:600636|Ensembl:ENSG00000164305|HPRD:02799|Vega:OTTHUMG00000133681 4 4q34 caspase 3, apoptosis-related cysteine peptidase protein-coding caspase 3, apoptosis-related cysteine peptidase A decrease in XIAP expression (mRNA and protein level) and caspase-3 protein levels and an increase in cleaved caspase-3 protein were observed in human ovarian granulosa cells transfected with pre-mir-23a, along with an increased occurrence of apoptosis. 1510 miR-23a hsa-miR-23a-3p,hsa-miR-23a-5p MIMAT0000078,MIMAT0004496 miRNA CASP7 apoptosis down Homo sapiens UVB-irradiated HaCaT cell 23158364 9606 840 CASP-7|CMH-1|ICE-LAP3|LICE2|MCH3 HGNC:1508|MIM:601761|Ensembl:ENSG00000165806|HPRD:03457|Vega:OTTHUMG00000019076 10 10q25 caspase 7, apoptosis-related cysteine peptidase protein-coding caspase 7, apoptosis-related cysteine peptidase Forced over-expression of miR-23a decreased the expression of UVB-induced topoisomerase-1caspase7STK4 at both the mRNA and protein levels, and these effects were reversed by down-regulation of miR-23a. 1511 miR-23a hsa-miR-23a-5p,hsa-miR-23a-3p MIMAT0004496,MIMAT0000078 miRNA XIAP apoptosis up Homo sapiens ischemic brain 21709246 9606 331 API3|BIRC4|IAP-3|ILP1|MIHA|XLP2|hIAP-3|hIAP3 HGNC:592|MIM:300079|Ensembl:ENSG00000101966|HPRD:02094|Vega:OTTHUMG00000022336 X Xq25 X-linked inhibitor of apoptosis protein-coding X-linked inhibitor of apoptosis E3 ubiquitin-protein liga XIAP is a previously uncharacterized target for miR 23a. miR-23a levels differed in male and female ischemic brains, providing evidence for sex specific miRNA expression in stroke. 1512 miR-23a hsa-miR-23a-3p,hsa-miR-23a-5p MIMAT0000078,MIMAT0004496 miRNA XIAP apoptosis down Homo sapiens varian granulosa cells 22653319 9606 331 API3|BIRC4|IAP-3|ILP1|MIHA|XLP2|hIAP-3|hIAP3 HGNC:592|MIM:300079|Ensembl:ENSG00000101966|HPRD:02094|Vega:OTTHUMG00000022336 X Xq25 X-linked inhibitor of apoptosis protein-coding X-linked inhibitor of apoptosis A decrease in XIAP expression (mRNA and protein level) and caspase-3 protein levels and an increase in cleaved caspase-3 protein were observed in human ovarian granulosa cells transfected with pre-mir-23a, along with an increased occurrence of apoptosis. 1513 miR-23b hsa-miR-23b-3p,hsa-miR-23b-5p MIMAT0000418,MIMAT0004587 miRNA AKT1 apoptosis up Homo sapiens prostate cancer cells 23074286 9606 207 AKT|CWS6|PKB|PKB-ALPHA|PRKBA|RAC|RAC-ALPHA HGNC:391|MIM:164730|Ensembl:ENSG00000142208|HPRD:01261|Vega:OTTHUMG00000170795 14 14q32.32 v-akt murine thymoma viral oncogene homolog 1 protein-coding v-akt murine thymoma viral oncogene homolog 1 Increased expression of miR-23b inhibited proliferation, colony formation, migration/invasion, and triggered G(0)-G(1) cell-cycle arrest and apoptosis in prostate cancer. 1514 miR-23b hsa-miR-23b-5p,hsa-miR-23b-3p MIMAT0004587,MIMAT0000418 miRNA PRODH apoptosis down Homo sapiens renal cancer cells 20562915 9606 5625 HSPOX2|PIG6|POX|PRODH1|PRODH2|TP53I6 HGNC:9453|MIM:606810|Ensembl:ENSG00000100033|HPRD:08433|Vega:OTTHUMG00000150163 22 22q11.21 proline dehydrogenase (oxidase) 1 protein-coding proline dehydrogenase (oxidase) 1 p53-induced gene 6 protei Ectopic overexpression of miR-23b in normal renal cells resulted in striking downregulation of POX, whereas POX expression increased markedly when endogenous miR-23b was knocked down by its antagomirs in renal cancer cells. Consistent with the POX-mediated tumor suppression pathway, these antagomirs induced ROS, inhibited HIF signaling and increased apoptosis. 1515 miR-23b hsa-miR-23b-3p,hsa-miR-23b-5p MIMAT0000418,MIMAT0004587 miRNA SRC apoptosis up Homo sapiens prostate cancer cells 23074286 9606 6714 ASV|SRC1|c-SRC|p60-Src HGNC:11283|MIM:190090|Ensembl:ENSG00000197122|HPRD:01819|Vega:OTTHUMG00000032417 20 20q12-q13 SRC proto-oncogene, non-receptor tyrosine kinase protein-coding SRC proto-oncogene, non-receptor tyrosine kinase Increased expression of miR-23b inhibited proliferation, colony formation, migration/invasion, and triggered G(0)-G(1) cell-cycle arrest and apoptosis in prostate cancer. 1516 miR-23b hsa-miR-23b-3p,hsa-miR-23b-5p MIMAT0000418,MIMAT0004587 miRNA ZEB1 apoptosis down Homo sapiens bladder cancer cell lines and tumor cells 23844063 9606 6935 AREB6|BZP|DELTAEF1|FECD6|NIL2A|PPCD3|TCF8|ZFHEP|ZFHX1A HGNC:11642|MIM:189909|Ensembl:ENSG00000148516|HPRD:01798|Vega:OTTHUMG00000017907 10 10p11.2 zinc finger E-box binding homeobox 1 protein-coding zinc finger E-box binding homeobox 1 Fluorescence activated cell sorting (FACS) analysis revealed that re-expression of miR-23b in bladder cancer cells induced G0/G1 cell cycle arrest and apoptosis while inhibiting cell migration and invasion. Luciferase reporter assays demonstrated that Zeb1, a crucial regulator of epithelial-to-mesenchymal transition (EMT), is a direct target of miR-23b in bladder cancer. 1517 miR-23b hsa-miR-23b-3p,hsa-miR-23b-5p MIMAT0000418,MIMAT0004587 miRNA apoptosis Homo sapiens glioma cells 22649212 9606 7428 RCA1|VHL1|pVHL|HRCA1 HGNC:12687|HPRD:01905|MIM:608537 3 3p25.3 von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase protein coding von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase Down-regulation of miR-23b triggered growth inhibition, induced apoptosis, and suppressed invasion of glioma in vitro. 1518 miR-24 hsa-miR-24-1-5p,hsa-miR-24-2-5p,hsa-miR-24-3p MIMAT0000079,MIMAT0004497,MIMAT0000080 miRNA BCL2 apoptosis down Homo sapiens breast cancer cells 22328513 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 apoptosis regulator Bcl-2 Ectopic expression of miR-195, miR-24-2 and miR-365-2 individually led to a significant reduction of the levels of BCL2 protein. 1519 miR-24 hsa-miR-24-1-5p,hsa-miR-24-3p,hsa-miR-24-2-5p MIMAT0000079,MIMAT0000080,MIMAT0004497 miRNA XIAP apoptosis down Homo sapiens cancer 22733138 9606 331 API3|BIRC4|IAP-3|ILP1|MIHA|XLP2|hIAP-3|hIAP3 HGNC:592|MIM:300079|Ensembl:ENSG00000101966|HPRD:02094|Vega:OTTHUMG00000022336 X Xq25 X-linked inhibitor of apoptosis protein-coding X-linked inhibitor of apoptosis Moreover, miR-24 overexpression can overcome apoptosis resistance in cancer cells via downregulation of XIAP expression, and the resulting cancer cell death induced by tumor necrosis factor-related apoptosis-inducing ligand is executed by the canonical caspase-mediated apoptosis pathway. 1520 miR-24 hsa-miR-24-1-5p,hsa-miR-24-3p,hsa-miR-24-2-5p MIMAT0000079,MIMAT0000080,MIMAT0004497 miRNA apoptosis Homo sapiens nasopharyngeal carcinoma?cell 25319395 9606 We found that miR24 inhibited NPC cell growth, promoted cell apoptosis, and suppressed the growth of NPC xenografts. We showed that miR24 was significantly downregulated in recurrent NPC tissues. 1521 miR-25 hsa-miR-25-5p,hsa-miR-25-3p MIMAT0004498,MIMAT0000081 miRNA E2F1 apoptosis down Homo sapiens gastric cancer cells 18328430 9606 1869 E2F-1|RBAP1|RBBP3|RBP3 HGNC:3113|MIM:189971|Ensembl:ENSG00000101412|HPRD:01806|Vega:OTTHUMG00000032265 20 20q11.2 E2F transcription factor 1 protein-coding E2F transcription factor 1 Here we provide evidence that the miR-106b-25 cluster, upregulated in a subset of human gastric tumors, is activated by E2F1 in parallel with its host gene, Mcm7. In turn, miR-106b and miR-93 regulate E2F1 expression, establishing a miRNA-directed negative feedback loop. Furthermore, upregulation of these miRNAs impairs the TGFbeta tumor suppressor pathway, interfering with the expression of CDKN1A (p21(Waf1/Cip1)) and BCL2L11 (Bim). 1522 miR-25 hsa-miR-25-3p,hsa-miR-25-5p MIMAT0004498,MIMAT0000081 miRNA RECK apoptosis down Homo sapiens Gastric 24078004 9606 8434 ST15 HGNC:11345|MIM:605227|Ensembl:ENSG00000122707|HPRD:05567|Vega:OTTHUMG00000019898 9 9p13.3 reversion-inducing-cysteine-rich protein with kazal motifs protein-coding reversion-inducing-cysteine-rich protein with kazal motifs Finally, reversion-inducing-cysteine-rich protein with kazal motifs (RECK) was found to be a target of miR-25. Overexpression of RECK could significantly reverse the oncogenic effect of miR-25. Taken together, miR-25 might promote GC cells growth and motility partially by targeting RECK. 1523 miR-26 hsa-miR-26a-5p,hsa-miR-26a-1-3p,hsa-miR-26b-5p,hsa-miR-26b-3p MIMAT0000082,MIMAT0004499,MIMAT0004500,MIMAT0000083 miRNA apoptosis Homo sapiens 22848262 9606 MiR-26, a functional miRNA, has received much attention from researchers in recent years. miRNAs may play crucial roles in numerous biological processes such as cell proliferation, apoptosis, tumorigenesis at different stages of non-tumor diseases, growth and development of normal tissues, and other biological processes. The expression of miR-26 has been found to be specific to different biological processes. Furthermore, its expression is frequently abnormal in tumors, indicating that miR-26 may play significant roles in tumor formation. Various reports exist regarding miR-26 involvement in non-tumor diseases, as well as the process of growth and development of normal tissues. In this review, we report findings of recent studies on the expression of miR-26 in different types of diseases and the process of growth and development and its predicted target genes in different tissue types. In conclusion, it is useful for researchers to understand the role of miR-26 in different biological processes. 1524 miR-26a hsa-miR-26a-5p,hsa-miR-26a-1-3p,hsa-miR-26a-2-3p MIMAT0000082,MIMAT0004499,MIMAT0004681 miRNA CHEK1 apoptosis down Homo sapiens breast| prostate 24336073 9606 1111 CHK1 HGNC:1925|MIM:603078|Ensembl:ENSG00000149554|HPRD:04356|Vega:OTTHUMG00000165853 11 11q24.2 checkpoint kinase 1 protein-coding checkpoint kinase 1 Collectively, our data provide a novel mechanism whereby p53 represses Chk1 and Wee1 expression, at least partially, via upregulation of miR-16 and miR-26a and thus sensitizes tumour cells to genotoxic therapies. 1525 miR-26a hsa-miR-26a-5p,hsa-miR-26a-1-3p MIMAT0000082,MIMAT0004499 miRNA SMAD1 apoptosis down Homo sapiens Aberrant smooth muscle cell 20857419 9606 4086 BSP-1|BSP1|JV4-1|JV41|MADH1|MADR1 HGNC:6767|MIM:601595|Ensembl:ENSG00000170365|HPRD:03356|Vega:OTTHUMG00000161592 4 4q31 SMAD family member 1 protein-coding SMAD family member 1 Dual-luciferase reporter assays demonstrated enhanced SMAD signaling with miRNA-26a inhibition, and the opposite effect with miRNA-26a overexpression in transfected human cells. Furthermore, inhibition of miRNA-26a increased gene expression of SMAD-1 and SMAD-4, while overexpression inhibited SMAD-1 1526 miR-26a hsa-miR-26a-5p,hsa-miR-26a-1-3p MIMAT0000082,MIMAT0004499 miRNA SMAD4 apoptosis down Homo sapiens Aberrant smooth muscle cell 20857419 9606 4089 DPC4|JIP|MADH4|MYHRS HGNC:6770|MIM:600993|Ensembl:ENSG00000141646|HPRD:02995|Vega:OTTHUMG00000132696 18 18q21.1 SMAD family member 4 protein-coding SMAD family member 4 Dual-luciferase reporter assays demonstrated enhanced SMAD signaling with miRNA-26a inhibition, and the opposite effect with miRNA-26a overexpression in transfected human cells. Furthermore, inhibition of miRNA-26a increased gene expression of SMAD-1 and SMAD-4, while overexpression inhibited SMAD-1 1527 miR-26a hsa-miR-26a-5p,hsa-miR-26a-1-3p MIMAT0000082,MIMAT0004499 miRNA TNFSF10 apoptosis down Homo sapiens NA 20230625 9606 8743 APO2L|Apo-2L|CD253|TL2|TRAIL HGNC:11925|MIM:603598|Ensembl:ENSG00000121858|HPRD:04670|Vega:OTTHUMG00000156917 3 3q26 tumor necrosis factor (ligand) superfamily, member 10 protein-coding tumor necrosis factor (ligand) superfamily, member 10 Transfection of mimics of miR-26a protects several cell types from TRAIL-induced cell death. 1528 miR-26a hsa-miR-26a-5p,hsa-miR-26a-1-3p MIMAT0000082,MIMAT0004499 miRNA apoptosis Homo sapiens biliary cell 19345069 9606 Quantitative PCR was employed to validate down-regulation of microRNA-122a (miR-122a) and miR-26a and the increased expression of miR-328 and miR-299-5p. The predicted targets of these miRNAs are known to affect cell proliferation, apoptosis, inflammation, oxidative stress, and metabolism. Our data are the first to demonstrate that PBC is characterized by altered expression of hepatic miRNA; however additional studies are required to demonstrate a causal link between those miRNA and the development of PBC. 1529 miR-26b hsa-miR-26b-5p,hsa-miR-26b-3p MIMAT0000083,MIMAT0004500 miRNA apoptosis down Homo sapiens hepatocellular carcinoma cell 24565101 9606 257397 NAP1|MAP3K7IP3 HGNC:30681|Ensembl:ENSG00000157625|HPRD:06738|MIM:300480|Vega:OTTHUMG00000021329 x Xp21.2 TGF-beta activated kinase 1|MAP3K7 binding protein 3 protein coding TGF-beta activated kinase 1|MAP3K7 binding protein 3 Subsequent investigations revealed that miR-26b inhibited the expression of TAK1 and TAB3, two positive regulators of NF-¦ÊB pathway, by binding to their 3'-untranslated region. 1530 miR-27 hsa-miR-27a-3p,hsa-miR-27a-5p,hsa-miR-27b-5p,hsa-miR-27b-3p MIMAT0000084,MIMAT0004501,MIMAT0004588,MIMAT0000419 miRNA FOXO1 apoptosis Homo sapiens endometrial adenocarcinoma 24746199 9606 2308 FKH1|FKHR|FOXO1A HGNC:3819|MIM:136533|Ensembl:ENSG00000150907|HPRD:00645|Vega:OTTHUMG00000016775 13 13q14.1 forkhead box O1 protein-coding forkhead box O1 In conclusion, we propose that the miR27-FOXO1 tandem inhibits apoptosis and represents an alternative pathway for tumor cell survival in PIK3CA-nonmutated EEC. 1531 miR-27a hsa-miR-27a-3p,hsa-miR-27a-5p MIMAT0000084,MIMAT0004501 miRNA ZBTB10 apoptosis down Homo sapiens MDA-MB-231 cell 22407812 9606 65986 RINZF HGNC:30953|Ensembl:ENSG00000205189|HPRD:15689|Vega:OTTHUMG00000155016 8 8q13-q21.1 zinc finger and BTB domain containing 10 protein-coding zinc finger and BTB domain containing 10 The BA-induced Sp1, Sp3, and Sp4 downregulation was accompanied by increased zinc finger ZBTB10 expression, a putative Sp-repressor and decreased microRNA-27a levels, a microRNA involved in the regulation of ZBTB10. 1532 miR-27a hsa-miR-27a-3p,hsa-miR-27a-5p MIMAT0000084,MIMAT0004501 miRNA ZBTB10 apoptosis down Homo sapiens colon cancer cells 23194063 9606 65986 RINZF HGNC:30953|Ensembl:ENSG00000205189|HPRD:15689|Vega:OTTHUMG00000155016 8 8q13-q21.1 zinc finger and BTB domain containing 10 protein-coding zinc finger and BTB domain containing 10 Curcumin and RL197 inhibited RKO and SW480 colon cancer cell growth and induced apoptosis,The mechanism of curcumin-/RL197-induced repression of Sp transcription factors was ROS-dependent and due to induction of the Sp repressors ZBTB10 and ZBTB4 and downregulation of microRNAs (miR)-27a, miR-20a and miR-17-5p that regulate these repressors. 1533 miR-27a hsa-miR-27a-3p,hsa-miR-27a-5p MIMAT0000084,MIMAT0004501 miRNA ZBTB4 apoptosis down Homo sapiens colon cancer cells 23194063 9606 57659 KAISO-L1|ZNF903 HGNC:23847|MIM:612308|Ensembl:ENSG00000174282|HPRD:11693|Vega:OTTHUMG00000108137 17 17p13.1 zinc finger and BTB domain containing 4 protein-coding zinc finger and BTB domain containing 4 Curcumin and RL197 inhibited RKO and SW480 colon cancer cell growth and induced apoptosis,The mechanism of curcumin-/RL197-induced repression of Sp transcription factors was ROS-dependent and due to induction of the Sp repressors ZBTB10 and ZBTB4 and downregulation of microRNAs (miR)-27a, miR-20a and miR-17-5p that regulate these repressors. 1534 miR-27b hsa-miR-27b-5p,hsa-miR-27b-3p MIMAT0004588,MIMAT0000419 miRNA CYP1B1 apoptosis down Homo sapiens cancer cells 25698578 9606 1545 CP1B|CYPIB1|GLC3A|P4501B1 HGNC:2597|MIM:601771|Ensembl:ENSG00000138061|HPRD:03464|Vega:OTTHUMG00000100970 2 2p22.2 cytochrome P450, family 1, subfamily B, polypeptide 1 protein-coding cytochrome P450, family 1, subfamily B, polypeptide 1 cytochrome P450, family 1, subfamily B, polypeptide 1 Functionally, miR-27b enhances drug response by activating p53-dependent apoptosis and reducing CYP1B1-mediated drug detoxification. 1535 miR-29 hsa-miR-29a-3p,hsa-miR-29b-3p,hsa-miR-29c-3p,hsa-miR-29a-5p,hsa-miR-29 MIMAT0000086 ,MIMAT0000100,MIMAT0000681,MIMAT00045 miRNA BCL2 apoptosis down Homo sapiens hepatocellular carcinoma cells 20041405 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 apoptosis regulator Bcl-2 Moreover, introduction of miR-29 dramatically repressed the ability of HCC cells to form tumor in nude mice. Subsequent investigation characterized two antiapoptotic molecules, Bcl-2 and Mcl-1, as direct targets of miR-29. Furthermore, silencing of Bcl-2 and Mcl-1 phenocopied the proapoptotic effect of miR-29, whereas overexpression of these proteins attenuated the effect of miR-29. 1536 miR-29 hsa-miR-29a-3p,hsa-miR-29b-3p,hsa-miR-29c-3p,hsa-miR-29a-5p,hsa-miR-29 MIMAT0000086 ,MIMAT0000100,MIMAT0000681,MIMAT00045 miRNA CDC42 apoptosis down Homo sapiens p53-positive breast cancer cells 19079265 9606 998 CDC42Hs|G25K HGNC:1736|MIM:116952|Ensembl:ENSG00000070831|HPRD:00309|Vega:OTTHUMG00000002753 1 1p36.1 cell division cycle 42 protein-coding cell division cycle 42 G25K GTP-binding protein| MiR-29 family members (miR-29a, miR-29b and miR-29c) upregulate p53 levels and induce apoptosis in a p53-dependent manner and directly suppress p85 alpha (the regulatory subunit of PI3 kinase) and CDC42 (a Rho family GTPase), both of which negatively regulate p53. 1537 miR-29 hsa-miR-29a-3p,hsa-miR-29b-3p,hsa-miR-29c-3p,hsa-miR-29a-5p,hsa-miR-29 MIMAT0000086 ,MIMAT0000100,MIMAT0000681,MIMAT00045 miRNA CDK6 apoptosis Homo sapiens HPV-infected cell 21503900 9606 1021 PLSTIRE HGNC:1777|MIM:603368|Ensembl:ENSG00000105810|HPRD:04533|Vega:OTTHUMG00000131697 7 7q21-q22 cyclin-dependent kinase 6 protein-coding cyclin-dependent kinase 6 miR-29 restrains cell cycle progression and induces apoptosis via YY1 and CDK6 promoting malignant transformation induced by HPV, although the abnormality of miR-29 in HPV-infected cells might be regulated in an indirect way. 1538 miR-29 hsa-miR-29a-3p,hsa-miR-29b-3p,hsa-miR-29c-3p,hsa-miR-29a-5p,hsa-miR-29 MIMAT0000086 ,MIMAT0000100,MIMAT0000681,MIMAT00045 miRNA DNMT3A apoptosis down Homo sapiens 20643754 9606 1788 DNMT3A2|M.HsaIIIA|TBRS HGNC:2978|MIM:602769|Ensembl:ENSG00000119772|HPRD:04141|Vega:OTTHUMG00000094777 2 2p23 DNA (cytosine-5-)-methyltransferase 3 alpha protein-coding DNA (cytosine-5-)-methyltransferase 3 alpha Upregulation of the miR-29 family resulted in decreased levels of its targets DNMT3a and MCL1, consequently affecting DNA methylation and apoptosis. Altered expression of miR-16 led to changes in expression of BCL2, suggesting modulation of apoptosis. 1539 miR-29 hsa-miR-29a-3p,hsa-miR-29b-3p,hsa-miR-29c-3p,hsa-miR-29a-5p,hsa-miR-29 MIMAT0000086 ,MIMAT0000100,MIMAT0000681,MIMAT00045 miRNA MCL1 apoptosis down Homo sapiens hepatocellular carcinoma cells 20041405 9606 4170 BCL2L3|EAT|MCL1-ES|MCL1L|MCL1S|Mcl-1|TM|bcl2-L-3|mcl1/EAT HGNC:6943|MIM:159552|Ensembl:ENSG00000143384|HPRD:08870|Vega:OTTHUMG00000034867 1 1q21 myeloid cell leukemia 1 protein-coding myeloid cell leukemia 1 apoptosis regulator Bcl-2 Moreover, introduction of miR-29 dramatically repressed the ability of HCC cells to form tumor in nude mice. Subsequent investigation characterized two antiapoptotic molecules, Bcl-2 and Mcl-1, as direct targets of miR-29. Furthermore, silencing of Bcl-2 and Mcl-1 phenocopied the proapoptotic effect of miR-29, whereas overexpression of these proteins attenuated the effect of miR-29. 1540 miR-29 hsa-miR-29a-3p,hsa-miR-29b-3p,hsa-miR-29c-3p,hsa-miR-29a-5p,hsa-miR-29 MIMAT0000086 ,MIMAT0000100,MIMAT0000681,MIMAT00045 miRNA MCL1 apoptosis down Homo sapiens 20643754 9606 4170 BCL2L3|EAT|MCL1-ES|MCL1L|MCL1S|Mcl-1|TM|bcl2-L-3|mcl1/EAT HGNC:6943|MIM:159552|Ensembl:ENSG00000143384|HPRD:08870|Vega:OTTHUMG00000034867 1 1q21 myeloid cell leukemia 1 protein-coding myeloid cell leukemia 1 Upregulation of the miR-29 family resulted in decreased levels of its targets DNMT3a and MCL1, consequently affecting DNA methylation and apoptosis. Altered expression of miR-16 led to changes in expression of BCL2, suggesting modulation of apoptosis. 1541 miR-29 hsa-miR-29a-3p,hsa-miR-29b-3p,hsa-miR-29c-3p,hsa-miR-29a-5p,hsa-miR-29 MIMAT0000086 ,MIMAT0000100,MIMAT0000681,MIMAT00045 miRNA PIK3R1 apoptosis down Homo sapiens p53-positive breast cancer cells 19079265 9606 5295 AGM7|GRB1|p85|p85-ALPHA HGNC:8979|MIM:171833|Ensembl:ENSG00000145675|HPRD:01381|Vega:OTTHUMG00000131251 5 5q13.1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) protein-coding phosphoinositide-3-kinase, regulatory subunit 1 (alpha) G25K GTP-binding protein| MiR-29 family members (miR-29a, miR-29b and miR-29c) upregulate p53 levels and induce apoptosis in a p53-dependent manner and directly suppress p85 alpha (the regulatory subunit of PI3 kinase) and CDC42 (a Rho family GTPase), both of which negatively regulate p53. 1542 miR-29 hsa-miR-29a-3p,hsa-miR-29b-3p,hsa-miR-29c-3p,hsa-miR-29a-5p,hsa-miR-29 MIMAT0000086 ,MIMAT0000100,MIMAT0000681,MIMAT00045 miRNA TP53 apoptosis up Homo sapiens p53-positive breast cancer cells 19079265 9606 7157 BCC7|LFS1|P53|TRP53 HGNC:11998|MIM:191170|Ensembl:ENSG00000141510|HPRD:01859|Vega:OTTHUMG00000162125 17 17p13.1 tumor protein p53 protein-coding tumor protein p53 G25K GTP-binding protein| MiR-29 family members (miR-29a, miR-29b and miR-29c) upregulate p53 levels and induce apoptosis in a p53-dependent manner and directly suppress p85 alpha (the regulatory subunit of PI3 kinase) and CDC42 (a Rho family GTPase), both of which negatively regulate p53. 1543 miR-29 hsa-miR-29a-3p,hsa-miR-29b-3p,hsa-miR-29c-3p,hsa-miR-29a-5p,hsa-miR-29 MIMAT0000086 ,MIMAT0000100,MIMAT0000681,MIMAT00045 miRNA TP53 apoptosis updown Homo sapiens 22248053 9606 7157 BCC7|LFS1|P53|TRP53 HGNC:11998|MIM:191170|Ensembl:ENSG00000141510|HPRD:01859|Vega:OTTHUMG00000162125 17 17p13.1 tumor protein p53 protein-coding tumor protein p53 YY1 inhibits the expression of both miR-29 and miR-206.70,71 These 2 miRs possess tumor-suppressive activities through activating p53 and promoting cell apoptosis, respectively 1544 miR-29 hsa-miR-29a-3p,hsa-miR-29b-3p,hsa-miR-29c-3p,hsa-miR-29a-5p,hsa-miR-29 MIMAT0000086 ,MIMAT0000100,MIMAT0000681,MIMAT00045 miRNA YY1 apoptosis Homo sapiens HPV-infected cell 21503900 9606 7528 DELTA|INO80S|NF-E1|UCRBP|YIN-YANG-1 HGNC:12856|MIM:600013|HPRD:02482 14 14q YY1 transcription factor protein-coding YY1 transcription factor miR-29 restrains cell cycle progression and induces apoptosis via YY1 and CDK6 promoting malignant transformation induced by HPV, although the abnormality of miR-29 in HPV-infected cells might be regulated in an indirect way. 1545 miR-29 hsa-miR-29a-3p,hsa-miR-29b-3p,hsa-miR-29c-3p,hsa-miR-29a-5p,hsa-miR-29 MIMAT0000086 ,MIMAT0000100,MIMAT0000681,MIMAT00045 miRNA apoptosis Homo sapiens atrial cell 23595377 9606 Samples of a trial tissue showed the abnormal pathohistological and ultrastructural changes, the accelerated fibrosis, and apoptosis with aging and/or in AF dogs. Compared to the adult group, the expressions of microRNAs-21 and -29 were significantly increased, whereas the expressions of microRNAs-1 and -133 showed obvious downregulation tendency in the aged group. 1546 miR-29 hsa-miR-29a-3p,hsa-miR-29b-3p,hsa-miR-29c-3p,hsa-miR-29a-5p,hsa-miR-29 MIMAT0000086 ,MIMAT0000100,MIMAT0000681,MIMAT00045 miRNA apoptosis Homo sapiens breast/colon cancer cell 24573597 9606 We next highlight the upstream regulatory pathway of miR-29 and describe the relationship between miR-29 and cancer in detail. As a tumor suppressor, miR-29 restrains cancer progression by promoting tumor cell apoptosis, by suppressing DNA methylation of tumor-suppressor genes, by reducing proliferation of tumors and by increasing chemosensitivity. However, as a tumor promoter, miR-29 mediates epithelial-mesenchymal transition (EMT) and promotes metastasis in breast cancer and colon cancer. Finally, we suggest that miR-29 represents a novel diagnostic and prognostic biomarker or a therapeutic target for cancer. 1547 miR-2909 hsa-miR-2909 MIMAT0013863 miRNA KLF4 apoptosis Homo sapiens T cell 25037230 9606 9314 EZF|GKLF HGNC:6348|MIM:602253|Ensembl:ENSG00000136826|Vega:OTTHUMG00000020449 9 9q31 Kruppel-like factor 4 (gut) protein-coding Kruppel-like factor 4 (gut) Moreover, the inability of miR-2909 to regulate KLF4 and its downstream genes controlling cell cycle and apoptosis in T-cell but not in B-ALL was verified by antagomiR-2909 transfection. 1548 miR-296 hsa-miR-296-3p,hsa-miR-296-5p MIMAT0000690,MIMAT0004679 miRNA ABCB1 apoptosis up Homo sapiens esophageal squamous cell 20485139 9606 5243 ABC20|CD243|CLCS|GP170|MDR1|P-GP|PGY1 HGNC:40|MIM:171050|Ensembl:ENSG00000085563|HPRD:01370|Vega:OTTHUMG00000023393 7 7q21.12 ATP-binding cassette, sub-family B (MDR/TAP), member 1 protein-coding ATP-binding cassette, sub-family B (MDR/TAP), member 1 MiR-296 could confer sensitivity of both P-glycoprotein-related and P-glycoprotein-nonrelated drugs on esophageal cancer cells, and might promote ADR-induced apoptosis, accompanied by increased accumulation and decreased releasing amount of ADR. Downregulation of miR-296 could significantly decrease the expression of P-glycoprotein, Bcl-2, and the transcription of MDR1, but up-regulate the expression of Bax. 1549 miR-296 hsa-miR-296-3p,hsa-miR-296-5p MIMAT0000690,MIMAT0004679 miRNA BAX apoptosis down Homo sapiens esophageal squamous cell 20485139 9606 581 BCL2L4 HGNC:959|MIM:600040|Ensembl:ENSG00000087088|HPRD:02498|Vega:OTTHUMG00000160476 19 19q13.3-q13.4 BCL2-associated X protein protein-coding BCL2-associated X protein MiR-296 could confer sensitivity of both P-glycoprotein-related and P-glycoprotein-nonrelated drugs on esophageal cancer cells, and might promote ADR-induced apoptosis, accompanied by increased accumulation and decreased releasing amount of ADR. Downregulation of miR-296 could significantly decrease the expression of P-glycoprotein, Bcl-2, and the transcription of MDR1, but up-regulate the expression of Bax. 1550 miR-296 hsa-miR-296-3p,hsa-miR-296-5p MIMAT0000690,MIMAT0004679 miRNA BCL2 apoptosis up Homo sapiens esophageal squamous cell 20485139 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 MiR-296 could confer sensitivity of both P-glycoprotein-related and P-glycoprotein-nonrelated drugs on esophageal cancer cells, and might promote ADR-induced apoptosis, accompanied by increased accumulation and decreased releasing amount of ADR. Downregulation of miR-296 could significantly decrease the expression of P-glycoprotein, Bcl-2, and the transcription of MDR1, but up-regulate the expression of Bax. 1551 miR-296 hsa-miR-296-3p,hsa-miR-296-5p MIMAT0000690,MIMAT0004679 miRNA apoptosis Homo sapiens HeLa cells 15741182 9606 We also identified miRNA that when inhibited increased the level of apoptosis (miR-1d, 7, 148, 204, 210, 216 and 296) and one miRNA that decreased apoptosis (miR-214) in HeLa cells. 1552 miR-296-5p hsa-miR-296-5p MIMAT0000690 miRNA BBC3 apoptosis down Homo sapiens 21633093 9606 27113 JFY-1|JFY1|PUMA HGNC:17868|MIM:605854|Ensembl:ENSG00000105327|HPRD:16165|Vega:OTTHUMG00000183489 19 19q13.3-q13.4 BCL2 binding component 3 protein-coding BCL2 binding component 3 Also miR-296-5p levels inversely varied with PUMA mRNA levels in human liver specimens. Our results implicate miR-296-5p in the regulation of PUMA expression during hepatic lipoapoptosis. 1553 miR-296-5p hsa-miR-296-5p MIMAT0000690 miRNA CASP3 apoptosis Homo sapiens temporal lobe 24751812 9606 836 CPP32|CPP32B|SCA-1 HGNC:1504|MIM:600636|Ensembl:ENSG00000164305|HPRD:02799|Vega:OTTHUMG00000133681 4 4q34 caspase 3, apoptosis-related cysteine peptidase protein-coding caspase 3, apoptosis-related cysteine peptidase Meanwhile, the levels of miR-423-3p and miR-296-5p were correlated with the activity of caspase-3, an apoptosis indicator. Additionally, the loading of miR-423-3p was increased in RNA-induced silencing complex whilst caspase-6, a target of miR-423-3p, was reduced in chronic TLE rats. Collectively, our findings suggest that miRNAs may exert anti-apoptotic effects in chronic TLE. 1554 miR-296-5p hsa-miR-296-5p MIMAT0000690 miRNA CDX1 apoptosis down Homo sapiens gastric cancer cell 23353818 9606 1044 - HGNC:1805|MIM:600746|Ensembl:ENSG00000113722|HPRD:02849|Vega:OTTHUMG00000169772 5 5q32 caudal type homeobox 1 protein-coding caudal type homeobox 1 Furthermore, we found that the extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation and the subsequent downstream changes in protein levels related to cell cycle and apoptosis partly account for the miR-296-5p-CDX1-induced GC growth promotion. In addition, the detection of miR-296-5p and expression of CDX1 in primary GC tissues and adjacent IM tissues revealed that miR-296-5p is inversely correlated with CDX1, further supporting our in vitro results. 1555 miR-298-5p hsa-miR-298 MIMAT0004901 miRNA IGF1R apoptosis down Homo sapiens mammalian pancreatic Ï« cell 23360399 9606 3480 CD221|IGFIR|IGFR|JTK13 HGNC:5465|MIM:147370|Ensembl:ENSG00000140443|HPRD:00932|Vega:OTTHUMG00000149851 15 15q26.3 insulin-like growth factor 1 receptor protein-coding insulin-like growth factor 1 receptor Altogether, high-throughput microRNA profiling, functional analysis with synthetic mimics and molecular characterization of modulated pathways strongly suggest that specific downregulation of miR-296-3p and miR-298-5p, coupled to upregulation of their targets as IGF1R¦Â and TNF¦Á, is a major determinant of mammalian pancreatic ¦Á cells resistance to apoptosis induction by cytokines. 1556 miR-298-5p hsa-miR-298 MIMAT0004901 miRNA TNF apoptosis down Homo sapiens mammalian pancreatic Ï« cell 23360399 9606 7124 DIF|TNF-alpha|TNFA|TNFSF2 HGNC:11892|MIM:191160|Ensembl:ENSG00000232810|HPRD:01855|Vega:OTTHUMG00000031194 6 6p21.3 tumor necrosis factor protein-coding tumor necrosis factor Altogether, high-throughput microRNA profiling, functional analysis with synthetic mimics and molecular characterization of modulated pathways strongly suggest that specific downregulation of miR-296-3p and miR-298-5p, coupled to upregulation of their targets as IGF1R¦Â and TNF¦Á, is a major determinant of mammalian pancreatic ¦Á cells resistance to apoptosis induction by cytokines. 1557 miR-299-5p hsa-miR-299-5p MIMAT0002890 miRNA apoptosis Homo sapiens biliary cell 19345069 9606 Quantitative PCR was employed to validate down-regulation of microRNA-122a (miR-122a) and miR-26a and the increased expression of miR-328 and miR-299-5p. The predicted targets of these miRNAs are known to affect cell proliferation, apoptosis, inflammation, oxidative stress, and metabolism. Our data are the first to demonstrate that PBC is characterized by altered expression of hepatic miRNA; however additional studies are required to demonstrate a causal link between those miRNA and the development of PBC. 1558 miR-29a hsa-miR-29a-3p,hsa-miR-29a-5p MIMAT0000086,MIMAT0004503 miRNA BCL2 apoptosis down Homo sapiens H9c2 cells 20164119 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 In contrast, overexpressing miR-29 promoted apoptosis and completely blocked the protective effect of PIO. Antagomirs against miR-29a or -29c significantly reduced myocardial infarct size and apoptosis in hearts subjected to IR injury. Western blot analyses demonstrated that Mcl-2, an anti-apoptotic Bcl-2 family member, was increased by miR-29 inhibition. 1559 miR-29a hsa-miR-29a-3p,hsa-miR-29a-5p MIMAT0000086,MIMAT0004503 miRNA BCL2 apoptosis down Homo sapiens osteosarcoma cells 23113351 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 miRNA-29 members induced apoptosis through p53 gene activation, the effect of miRNA-29a on osteoblastic cells was independent on p53 expression level. Moreover, Bcl-2 and Mcl-1 were earlier demonstrated to be the direct targets of miRNA-29 in many types of cancer tissues and cancers. In addition, enhanced expression of miRNA-29a increased the expression of two tumor suppressor genes, E2F1 and E2F3. 1560 miR-29a hsa-miR-29a-3p,hsa-miR-29a-5p MIMAT0000086,MIMAT0004503 miRNA E2F1 apoptosis up Homo sapiens osteosarcoma cells 23113351 9606 1869 E2F-1|RBAP1|RBBP3|RBP3 HGNC:3113|MIM:189971|Ensembl:ENSG00000101412|HPRD:01806|Vega:OTTHUMG00000032265 20 20q11.2 E2F transcription factor 1 protein-coding E2F transcription factor 1 miRNA-29 members induced apoptosis through p53 gene activation, the effect of miRNA-29a on osteoblastic cells was independent on p53 expression level. Moreover, Bcl-2 and Mcl-1 were earlier demonstrated to be the direct targets of miRNA-29 in many types of cancer tissues and cancers. In addition, enhanced expression of miRNA-29a increased the expression of two tumor suppressor genes, E2F1 and E2F3. 1561 miR-29a hsa-miR-29a-3p,hsa-miR-29a-5p MIMAT0000086,MIMAT0004503 miRNA E2F3 apoptosis up Homo sapiens osteosarcoma cells 23113351 9606 1871 E2F-3 HGNC:3115|MIM:600427|Ensembl:ENSG00000112242|HPRD:02693|Vega:OTTHUMG00000016389 6 6p22 E2F transcription factor 3 protein-coding E2F transcription factor 3 miRNA-29 members induced apoptosis through p53 gene activation, the effect of miRNA-29a on osteoblastic cells was independent on p53 expression level. Moreover, Bcl-2 and Mcl-1 were earlier demonstrated to be the direct targets of miRNA-29 in many types of cancer tissues and cancers. In addition, enhanced expression of miRNA-29a increased the expression of two tumor suppressor genes, E2F1 and E2F3. 1562 miR-29a hsa-miR-29a-3p,hsa-miR-29a-5p MIMAT0000086,MIMAT0004503 miRNA MCL1 apoptosis down Homo sapiens H9c2 cells 20164119 9606 4170 BCL2L3|EAT|MCL1-ES|MCL1L|MCL1S|Mcl-1|TM|bcl2-L-3|mcl1/EAT HGNC:6943|MIM:159552|Ensembl:ENSG00000143384|HPRD:08870|Vega:OTTHUMG00000034867 1 1q21 myeloid cell leukemia 1 protein-coding myeloid cell leukemia 1 In contrast, overexpressing miR-29 promoted apoptosis and completely blocked the protective effect of PIO. Antagomirs against miR-29a or -29c significantly reduced myocardial infarct size and apoptosis in hearts subjected to IR injury. Western blot analyses demonstrated that Mcl-1, an anti-apoptotic Bcl-2 family member, was increased by miR-29 inhibition. 1563 miR-29a hsa-miR-29a-3p,hsa-miR-29a-5p MIMAT0000086,MIMAT0004503 miRNA MCL1 apoptosis down Homo sapiens osteosarcoma cells 23113351 9606 4170 BCL2L3|EAT|MCL1-ES|MCL1L|MCL1S|Mcl-1|TM|bcl2-L-3|mcl1/EAT HGNC:6943|MIM:159552|Ensembl:ENSG00000143384|HPRD:08870|Vega:OTTHUMG00000034867 1 1q21 myeloid cell leukemia 1 protein-coding myeloid cell leukemia 1 miRNA-29 members induced apoptosis through p53 gene activation, the effect of miRNA-29a on osteoblastic cells was independent on p53 expression level. Moreover, Bcl-2 and Mcl-1 were earlier demonstrated to be the direct targets of miRNA-29 in many types of cancer tissues and cancers. In addition, enhanced expression of miRNA-29a increased the expression of two tumor suppressor genes, E2F1 and E2F3. 1564 miR-29a hsa-miR-29a-3p,hsa-miR-29a-5p MIMAT0000086,MIMAT0004503 miRNA MCL1 apoptosis down Homo sapiens epithelial cells 25674218 9606 4170 BCL2L3|EAT|MCL1-ES|MCL1L|MCL1S|Mcl-1|TM|bcl2-L-3|mcl1/EAT HGNC:6943|MIM:159552|Ensembl:ENSG00000143384|HPRD:08870|Vega:OTTHUMG00000034867 1 1q21 myeloid cell leukemia 1 protein-coding myeloid cell leukemia 1 Knockout of Mcl-1 caused apoptosis of the colonic epithelial HT29 cells. In addition, miR-29a regulated intestinal epithelial apoptosis by down-regulating the expression of Mcl-1. 1565 miR-29a hsa-miR-29a-3p,hsa-miR-29a-5p MIMAT0000086,MIMAT0004503 miRNA PPM1D apoptosis Homo sapiens HepG-2 cell 21175813 9606 8493 PP2C-DELTA|WIP1 HGNC:9277|MIM:605100|HPRD:05482 17 17q23.2 protein phosphatase, Mg2+/Mn2+ dependent, 1D protein-coding protein phosphatase, Mg2+/Mn2+ dependent, 1D Among them, miR-29a showed a positive therapeutic effect in liver cancer cells by inhibiting cell growth and inducing cell apoptosis, and PPM1D was confirmed to be the target gene of miR-29a. Furthermore, a synergy effect was detected between miR-29a and arsenic trioxide. 1566 miR-29a hsa-miR-29a-3p,hsa-miR-29a-5p MIMAT0000086,MIMAT0004503 miRNA apoptosis down Homo sapiens glioma cell 24595468 9606 871 CBP1|CBP2|OI10|gp46|AsTP3|SERPINH1|PIG14|PPROM|RA-A47|SERPINH2 HGNC:1546|Ensembl:ENSG00000149257|HPRD:02968|MIM:600943|Vega:OTTHUMG00000165362 11 11q13.5 serpin peptidase inhibitor, clade H (heat shock protein 47), member 1, (collagen binding protein 1) protein coding serpin peptidase inhibitor, clade H (heat shock protein 47), member 1, (collagen binding protein 1) he results suggested that the expression of HSP47 is regulated by miR-29a. Finally, stable knockdown of HSP47 using shRNA inhibits glioma tumor growth and induces apoptosis in mice models in vivo. Therefore, our data suggested that HSP47 regulated by miR-29a to enhance glioma tumor growth and invasion. 1567 miR-29b hsa-miR-29b-3p,hsa-miR-29b-1-5p,hsa-miR-29b-2-5p MIMAT0000100,MIMAT0004514,MIMAT0004515 miRNA ABL1 apoptosis down Homo sapiens CML patient samples 23428668 9606 25 ABL|JTK7|bcr/abl|c-ABL|c-ABL1|p150|v-abl HGNC:76|MIM:189980|Ensembl:ENSG00000097007|HPRD:01809|Vega:OTTHUMG00000020813 9 9q34.1 ABL proto-oncogene 1, non-receptor tyrosine kinase protein-coding ABL proto-oncogene 1, non-receptor tyrosine kinase miR-29b significantly suppresses the activity of a luciferase reporter containing ABL1-3'UTR and this activity is not observed in cells transfected with mutated ABL1-3'UTR. 1568 miR-29b hsa-miR-29b-3p,hsa-miR-29b-1-5p,hsa-miR-29b-2-5p MIMAT0000100,MIMAT0004514,MIMAT0004515 miRNA BCL2 apoptosis down Homo sapiens plasmacytoid dendritic cell 23894561 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 Bioinformatics analysis and functional studies indicated that miR-29b and miR-29c were 2 key miRNAs involved in TLR-inhibited GC-induced pDC apoptosis. Furthermore, both of these miRNAs promoted pDC apoptosis by directly targeting Mcl-1 and Bcl-2 in human primary pDCs. Our findings provide new targets that could improve the efficacy of GCs for the treatment of SLE. 1569 miR-29b hsa-miR-29b-3p,hsa-miR-29b-1-5p,hsa-miR-29b-2-5p MIMAT0000100,MIMAT0004514,MIMAT0004515 miRNA ITGB1 apoptosis down Homo sapiens trophoblast cells 22716646 9606 3688 CD29|FNRB|GPIIA|MDF2|MSK12|VLA-BETA|VLAB HGNC:6153|MIM:135630|Ensembl:ENSG00000150093|HPRD:00628|Vega:OTTHUMG00000017928 10 10p11.2 integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12) protein-coding integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12) We found that miR-29b induced apoptosis and inhibited invasion and angiogenesis of trophoblast cells. Further studies confirmed that miR-29b regulated the expression of MCL1 (myeloid cell leukaemia sequence 1), MMP2 (encoding matrix metallproteinase 2), VEGFA (vascular endothelial growth factor A) and ITGB1 (integrin ¦Â1) genes by directly binding to their 3'-UTRs (untranslated regions). Moreover, we identified that there was an inverse correlation between miR-29b and its target genes in subjects with PE. 1570 miR-29b hsa-miR-29b-3p,hsa-miR-29b-1-5p,hsa-miR-29b-2-5p MIMAT0000100,MIMAT0004514,MIMAT0004515 miRNA MCL1 apoptosis down Homo sapiens trophoblast cells 22716646 9606 4170 BCL2L3|EAT|MCL1-ES|MCL1L|MCL1S|Mcl-1|TM|bcl2-L-3|mcl1/EAT HGNC:6943|MIM:159552|Ensembl:ENSG00000143384|HPRD:08870|Vega:OTTHUMG00000034867 1 1q21 myeloid cell leukemia 1 protein-coding myeloid cell leukemia 1 We found that miR-29b induced apoptosis and inhibited invasion and angiogenesis of trophoblast cells. Further studies confirmed that miR-29b regulated the expression of MCL1 (myeloid cell leukaemia sequence 1), MMP2 (encoding matrix metallproteinase 2), VEGFA (vascular endothelial growth factor A) and ITGB1 (integrin ¦Â1) genes by directly binding to their 3'-UTRs (untranslated regions). Moreover, we identified that there was an inverse correlation between miR-29b and its target genes in subjects with PE. 1571 miR-29b hsa-miR-29b-3p,hsa-miR-29b-1-5p,hsa-miR-29b-2-5p MIMAT0000100,MIMAT0004514,MIMAT0004515 miRNA MCL1 apoptosis down Homo sapiens plasmacytoid dendritic cell 23894561 9606 4170 BCL2L3|EAT|MCL1-ES|MCL1L|MCL1S|Mcl-1|TM|bcl2-L-3|mcl1/EAT HGNC:6943|MIM:159552|Ensembl:ENSG00000143384|HPRD:08870|Vega:OTTHUMG00000034867 1 1q21 myeloid cell leukemia 1 protein-coding myeloid cell leukemia 1 Bioinformatics analysis and functional studies indicated that miR-29b and miR-29c were 2 key miRNAs involved in TLR-inhibited GC-induced pDC apoptosis. Furthermore, both of these miRNAs promoted pDC apoptosis by directly targeting Mcl-1 and Bcl-2 in human primary pDCs. Our findings provide new targets that could improve the efficacy of GCs for the treatment of SLE. 1572 miR-29b hsa-miR-29b-3p,hsa-miR-29b-1-5p,hsa-miR-29b-2-5p MIMAT0000100,MIMAT0004514,MIMAT0004515 miRNA MMP2 apoptosis down Homo sapiens trophoblast cells 22716646 9606 4313 CLG4|CLG4A|MMP-II|MONA|TBE-1 HGNC:7166|MIM:120360|Ensembl:ENSG00000087245|HPRD:00386|Vega:OTTHUMG00000133202 16 16q13-q21 matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase) protein-coding matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase) We found that miR-29b induced apoptosis and inhibited invasion and angiogenesis of trophoblast cells. Further studies confirmed that miR-29b regulated the expression of MCL1 (myeloid cell leukaemia sequence 1), MMP2 (encoding matrix metallproteinase 2), VEGFA (vascular endothelial growth factor A) and ITGB1 (integrin ¦Â1) genes by directly binding to their 3'-UTRs (untranslated regions). Moreover, we identified that there was an inverse correlation between miR-29b and its target genes in subjects with PE. 1573 miR-29b hsa-miR-29b-3p,hsa-miR-29b-1-5p,hsa-miR-29b-2-5p MIMAT0000100,MIMAT0004514,MIMAT0004515 miRNA SP1 apoptosis up Homo sapiens multiple myeloma cells 23190608 9606 6667 - HGNC:11205|MIM:189906|Ensembl:ENSG00000185591|HPRD:01796|Vega:OTTHUMG00000170047 12 12q13.1 Sp1 transcription factor protein-coding Sp1 transcription factor MicroRNAs (miRNAs) with tumor-suppressor potential might have therapeutic applications in multiple myeloma (MM) through the modulation of still undiscovered molecular pathways. We identified Sp1, a transcription factor endowed with oncogenic activity, as a negative regulator of miR-29b expression in MM cells. 1574 miR-29b hsa-miR-29b-3p,hsa-miR-29b-1-5p,hsa-miR-29b-2-5p MIMAT0000100,MIMAT0004514,MIMAT0004515 miRNA VEGFA apoptosis down Homo sapiens trophoblast cells 22716646 9606 7422 MVCD1|VEGF|VPF HGNC:12680|MIM:192240|Ensembl:ENSG00000112715|HPRD:01889|Vega:OTTHUMG00000014745 6 6p12 vascular endothelial growth factor A protein-coding vascular endothelial growth factor A We found that miR-29b induced apoptosis and inhibited invasion and angiogenesis of trophoblast cells. Further studies confirmed that miR-29b regulated the expression of MCL1 (myeloid cell leukaemia sequence 1), MMP2 (encoding matrix metallproteinase 2), VEGFA (vascular endothelial growth factor A) and ITGB1 (integrin ¦Â1) genes by directly binding to their 3'-UTRs (untranslated regions). Moreover, we identified that there was an inverse correlation between miR-29b and its target genes in subjects with PE. 1575 miR-29b-3p hsa-miR-29b-3p MIMAT0000100 miRNA apoptosis Homo sapiens epidermal stem cell 25373715 9606 RT-qPCR results confirmed the upregulation of hsa-miR-197-5p and the downregulation of hsa-miR-29b-3p, which were consistent with the microarray results. miRNA target prediction indicated that the miRNA expression levels correlated with cell proliferation, differentiation, apoptosis and senescence. 1576 miR-29c hsa-miR-29c-3p,hsa-miR-29c-5p MIMAT0000681,MIMAT0004673 miRNA BCL2 apoptosis down Homo sapiens H9c2 cells 20164119 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 In contrast, overexpressing miR-29 promoted apoptosis and completely blocked the protective effect of PIO. Antagomirs against miR-29a or -29c significantly reduced myocardial infarct size and apoptosis in hearts subjected to IR injury. Western blot analyses demonstrated that Mcl-2, an anti-apoptotic Bcl-2 family member, was increased by miR-29 inhibition. 1577 miR-29c hsa-miR-29c-3p,hsa-miR-29c-5p MIMAT0000681,MIMAT0004673 miRNA BCL2 apoptosis down Homo sapiens NPC tissues and cell lines 23142283 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 Our further in vitro and in vivo studies illustrated ectopic restoration of miR-29c substantially enhanced the sensitivity of NPC cells to IR and cisplatin treatment by promoting apoptosis. Furthermore, we detected miR-29c repressed expression of anti-apoptotic factors, Mcl-1 and Bcl-2 in NPC tissues and cell lines. 1578 miR-29c hsa-miR-29c-3p,hsa-miR-29c-5p MIMAT0000681,MIMAT0004673 miRNA BCL2 apoptosis down Homo sapiens plasmacytoid dendritic cell 23894561 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 Bioinformatics analysis and functional studies indicated that miR-29b and miR-29c were 2 key miRNAs involved in TLR-inhibited GC-induced pDC apoptosis. Furthermore, both of these miRNAs promoted pDC apoptosis by directly targeting Mcl-1 and Bcl-2 in human primary pDCs. Our findings provide new targets that could improve the efficacy of GCs for the treatment of SLE. 1579 miR-29c hsa-miR-29c-3p,hsa-miR-29c-5p MIMAT0004673,MIMAT0000681 miRNA BCL2 apoptosis down Homo sapiens BIU-87 cell 24870742 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 Exosome-derived microRNA-29c induces apoptosis of BIU-87 cells by down regulating BCL-2 and MCL-1. 1580 miR-29c hsa-miR-29c-3p,hsa-miR-29c-5p MIMAT0000681,MIMAT0004673 miRNA BCL2L2 apoptosis up Homo sapiens adenocarcinomic human alveolar basal epithelial cells 22850539 9606 599 BCL-W|BCL2-L-2|BCLW|PPP1R51 HGNC:995|MIM:601931|Ensembl:ENSG00000129473|HPRD:03569|Vega:OTTHUMG00000028738 14 14q11.2-q12 BCL2-like 2 protein-coding BCL2-like 2 Transfection of miR-29c inhibitor abolished both suppression of BCL2L2 protein expression and A549 cells apoptosis induced by influenza A virus. 1581 miR-29c hsa-miR-29c-3p,hsa-miR-29c-5p MIMAT0000681,MIMAT0004673 miRNA MCL1 apoptosis down Homo sapiens H9c2 cells 20164119 9606 4170 BCL2L3|EAT|MCL1-ES|MCL1L|MCL1S|Mcl-1|TM|bcl2-L-3|mcl1/EAT HGNC:6943|MIM:159552|Ensembl:ENSG00000143384|HPRD:08870|Vega:OTTHUMG00000034867 1 1q21 myeloid cell leukemia 1 protein-coding myeloid cell leukemia 1 In contrast, overexpressing miR-29 promoted apoptosis and completely blocked the protective effect of PIO. Antagomirs against miR-29a or -29c significantly reduced myocardial infarct size and apoptosis in hearts subjected to IR injury. Western blot analyses demonstrated that Mcl-1, an anti-apoptotic Bcl-2 family member, was increased by miR-29 inhibition. 1582 miR-29c hsa-miR-29c-3p,hsa-miR-29c-5p MIMAT0000681,MIMAT0004673 miRNA MCL1 apoptosis down Homo sapiens NPC tissues and cell lines 23142283 9606 4170 BCL2L3|EAT|MCL1-ES|MCL1L|MCL1S|Mcl-1|TM|bcl2-L-3|mcl1/EAT HGNC:6943|MIM:159552|Ensembl:ENSG00000143384|HPRD:08870|Vega:OTTHUMG00000034867 1 1q21 myeloid cell leukemia 1 protein-coding myeloid cell leukemia 1 Our further in vitro and in vivo studies illustrated ectopic restoration of miR-29c substantially enhanced the sensitivity of NPC cells to IR and cisplatin treatment by promoting apoptosis. Furthermore, we detected miR-29c repressed expression of anti-apoptotic factors, Mcl-1 and Bcl-2 in NPC tissues and cell lines. 1583 miR-29c hsa-miR-29c-3p,hsa-miR-29c-5p MIMAT0000681,MIMAT0004673 miRNA MCL1 apoptosis down Homo sapiens plasmacytoid dendritic cell 23894561 9606 4170 BCL2L3|EAT|MCL1-ES|MCL1L|MCL1S|Mcl-1|TM|bcl2-L-3|mcl1/EAT HGNC:6943|MIM:159552|Ensembl:ENSG00000143384|HPRD:08870|Vega:OTTHUMG00000034867 1 1q21 myeloid cell leukemia 1 protein-coding myeloid cell leukemia 1 Bioinformatics analysis and functional studies indicated that miR-29b and miR-29c were 2 key miRNAs involved in TLR-inhibited GC-induced pDC apoptosis. Furthermore, both of these miRNAs promoted pDC apoptosis by directly targeting Mcl-1 and Bcl-2 in human primary pDCs. Our findings provide new targets that could improve the efficacy of GCs for the treatment of SLE. 1584 miR-29c hsa-miR-29c-3p,hsa-miR-29c-5p MIMAT0004673,MIMAT0000681 miRNA MCL1 apoptosis down Homo sapiens BIU-87 cell 24870742 9606 4170 BCL2L3|EAT|MCL1-ES|MCL1L|MCL1S|Mcl-1|TM|bcl2-L-3|mcl1/EAT HGNC:6943|MIM:159552|Ensembl:ENSG00000143384|HPRD:08870|Vega:OTTHUMG00000034867 1 1q21 myeloid cell leukemia 1 protein-coding myeloid cell leukemia 1 Exosome-derived microRNA-29c induces apoptosis of BIU-87 cells by down regulating BCL-2 and MCL-1. 1585 miR-30 hsa-miR-30a-5p,hsa-miR-30a-3p,hsa-miR-30c-5p,hsa-miR-30d-5p,hsa-miR-30 MIMAT0000087,MIMAT0000088,MIMAT0000244,MIMAT000024 miRNA ITGB3 apoptosis down Homo sapiens tumor-initiating cell (T-ICs) 20498642 9606 3690 BDPLT16|BDPLT2|CD61|GP3A|GPIIIa|GT HGNC:6156|MIM:173470|Ensembl:ENSG00000259207|HPRD:01428|Vega:OTTHUMG00000171956 17 17q21.32 integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61) protein-coding integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61) Similar to let-7, mir-30 is reduced in BT-ICs, and the protein level of Ubc9 (ubiquitin-conjugating enzyme 9) and ITGB3 (integrin beta3), the target genes of mir-30, is markedly upregulated. Enforced constitutive expression of mir-30 in BT-ICs inhibits their self-renewal capacity by reducing Ubc9, and induces apoptosis through silencing ITGB3. 1586 miR-30 hsa-miR-30a-5p,hsa-miR-30a-3p,hsa-miR-30c-5p,hsa-miR-30c-2-3p,hsa-miR-30d-5p,hsa-miR-30d-3p,hsa-miR-30b-5p,hsa-miR-30b-3p,hsa-miR-30c-1-3p,hsa-miR-30e-5p,hsa-miR-30e-3p MIMAT0000087,MIMAT0000088,MIMAT0000244,MIMAT0004550,MIMAT0000245,MIMAT0004551,MIMAT0000420,MIMAT0004589,MIMAT0004674,MIMAT0000692,MIMAT0000693, miRNA TP53 apoptosis down Homo sapiens 20062521 9606 7157 BCC7|LFS1|P53|TRP53 HGNC:11998|MIM:191170|Ensembl:ENSG00000141510|HPRD:01859|Vega:OTTHUMG00000162125 17 17p13.1 tumor protein p53 protein-coding tumor protein p53 In exploring the underlying molecular mechanism, we identified that miR-30 family members can suppress p53 expression. In response to the apoptotic stimulation, the expression levels of miR-30 family members were reduced, whereas p53 was upregulated. p53 transcriptionally activated the mitochondrial fission protein, dynamin-related protein-1 (Drp1). The latter conveyed the apoptotic signal of p53 by initiating the mitochondrial fission program. 1587 miR-30 hsa-miR-30a-5p,hsa-miR-30a-3p,hsa-miR-30c-5p,hsa-miR-30d-5p,hsa-miR-30 MIMAT0000087,MIMAT0000088,MIMAT0000244,MIMAT000024 miRNA TP53 apoptosis down Homo sapiens 25137026 9606 7157 BCC7|LFS1|P53|TRP53 HGNC:11998|MIM:191170|Ensembl:ENSG00000141510|HPRD:01859|Vega:OTTHUMG00000162125 17 17p13.1 tumor protein p53 protein-coding tumor protein p53 Tp53 is a validated target of miR-30 whose levels fall under ischemic conditions.The concomitant decrease in p53 protein content reduces Bax expression and limits mitochondrial membrane depolarization resulting in preserved mitochondrial function and decreased apoptosis and necrosis extent in the area at risk (AAR). 1588 miR-300 hsa-miR-300 MIMAT0004903 miRNA apoptosis Homo sapiens gastric cancer cell 24919435 9606 We predicted the targets of the two miRNAs with TargetScan and classified all the candidate targets with Gene Ontology, which indicated that both miR-300 and miR-642 potentially regulate cellular radiation response by modulating apoptosis, cell cycle regulation and DNA damage and repair pathway-related genes. 1589 miR-301a hsa-miR-301a-5p,hsa-miR-301a-3p MIMAT0022696,MIMAT0000688 miRNA MEOX2 apoptosis down Homo sapiens HCC cell 22373864 9606 4223 GAX|MOX2 HGNC:7014|MIM:600535|Ensembl:ENSG00000106511|HPRD:02760|Vega:OTTHUMG00000152390 7 7p22.1-p21.3 mesenchyme homeobox 2 protein-coding mesenchyme homeobox 2 MiR-301a was significantly upregulated and Gax was downregulated in HCC samples compared with in the matching nontumoral tissues. Inhibiting miR-301a expression caused the upregulation of Gax and repressed NF-¦ÊB expression. We have shown that miR-301a plays an important role in increasing proliferation, migration and invasion and in inhibiting apoptosis of HCC cells. 1590 miR-301a hsa-miR-301a-5p,hsa-miR-301a-3p MIMAT0022696,MIMAT0000688 miRNA NFKB1 apoptosis up Homo sapiens HCC cell 22373864 9606 4790 EBP-1|KBF1|NF-kB1|NF-kappa-B|NF-kappaB|NFKB-p105|NFKB-p50|NFkappaB|p105|p50 HGNC:7794|MIM:164011|Ensembl:ENSG00000109320|HPRD:01238|Vega:OTTHUMG00000161080 4 4q24 nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 protein-coding nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 MiR-301a was significantly upregulated and Gax was downregulated in HCC samples compared with in the matching nontumoral tissues. Inhibiting miR-301a expression caused the upregulation of Gax and repressed NF-¦ÊB expression. We have shown that miR-301a plays an important role in increasing proliferation, migration and invasion and in inhibiting apoptosis of HCC cells. 1591 miR-301a hsa-miR-301a-5p,hsa-miR-301a-3p MIMAT0022696,MIMAT0000688 miRNA PRKAA1 apoptosis down Homo sapiens osteosarcoma cell 25727016 9606 5562 AMPK|AMPKa1 HGNC:9376|MIM:602739|Ensembl:ENSG00000132356|HPRD:04115|Vega:OTTHUMG00000162269 5 5p12 protein kinase, AMP-activated, alpha 1 catalytic subunit protein-coding protein kinase, AMP-activated, alpha 1 catalytic subunit MicroRNA-301a modulates doxorubicin resistance in osteosarcoma cells by targeting AMP-activated protein kinase alpha 1. Luciferase reporter assay identified AMPK¦Á1 as direct target gene of miR-301a. Notably, miR-301a reduced doxorubicin-induced cell apoptosis whereas anti-miR-301a enhanced apoptosis in OS cells, suggesting that up-regulation of miR-301a contributed to chemoresistance of OS cells. 1592 miR-302 hsa-miR-302a-5p,hsa-miR-302a-3p,hsa-miR-302b-5p,hsa-miR-302b-3p,hsa-miR-302c-5p,hsa-miR-302c-3p,hsa-miR-302d-3p,hsa-miR-302d-5p,hsa-miR-302e,hsa-miR-302f MIMAT0000683,MIMAT0000684,MIMAT0000714,MIMAT0000715,MIMAT0000716,MIMAT0000717,MIMAT0000718,MIMAT0004685,MIMAT0005931,MIMAT0005932 miRNA BCL2L11 apoptosis Homo sapiens stem cell 25184675 9606 10018 BAM|BIM|BOD HGNC:994|MIM:603827|Ensembl:ENSG00000153094|HPRD:04828|Vega:OTTHUMG00000131256 2 2q13 BCL2-like 11 (apoptosis facilitator) protein-coding BCL2-like 11 (apoptosis facilitator) Moreover, we found that three miRNA families, miR-20, miR-92, and miR-302, control the mitochondrial apoptotic machinery by fine-tuning the levels of expression of the proapoptotic protein BIM. 1593 miR-302 hsa-miR-302a-5p,hsa-miR-302a-3p,hsa-miR-302b-5p,hsa-miR-302b-3p,hsa-miR-302c-5p,hsa-miR-302c-3p,hsa-miR-302d-3p,hsa-miR-302d-5p,hsa-miR-302e,hsa-miR-302f MIMAT0000683,MIMAT0000684,MIMAT0000714,MIMAT0000715,MIMAT0000716,MIMAT0000717,MIMAT0000718,MIMAT0004685,MIMAT0005931,MIMAT0005932 miRNA apoptosis down Homo sapiens embryonic stem cell 25501598 9606 Suppression of epithelial-mesenchymal transition and apoptotic pathways by miR-294/302 family synergistically blocks let-7-induced silencing of self-renewal in embryonic stem cells. 1594 miR-302a hsa-miR-302a-5p,hsa-miR-302a-3p MIMAT0000683,MIMAT0000684 miRNA BMI1 apoptosis down Homo sapiens AGS/HepG2 cell 24861464 9606 648 FLVI2/BMI1|PCGF4|RNF51 HGNC:1066|MIM:164831|Ensembl:ENSG00000168283|HPRD:01277|Vega:OTTHUMG00000017807 10 10p11.23 BMI1 proto-oncogene, polycomb ring finger protein-coding BMI1 proto-oncogene, polycomb ring finger MiR-302a and miR-4448 were markedly upregulated by treatment with SAHA and DZNep, respectively. DYRK1A, CDK2, BMI-1 and Girdin, which are targets of miR-1246, miR-302a and miR-4448, were suppressed by treatment with SAHA and DZNep, leading to apoptosis, cell cycle arrest and reduced migration of AGS and HepG2 cells. 1595 miR-302a hsa-miR-302a-5p,hsa-miR-302a-3p MIMAT0000683,MIMAT0000684 miRNA CCDC88A apoptosis down Homo sapiens AGS/HepG2 cell 24861464 9606 55704 APE|GIRDIN|GIV|GRDN|HkRP1|KIAA1212 HGNC:25523|MIM:609736|Ensembl:ENSG00000115355|HPRD:10051|HPRD:11131|Vega:OTTHUMG00000151915 2 2p16.1 coiled-coil domain containing 88A protein-coding coiled-coil domain containing 88A MiR-302a and miR-4448 were markedly upregulated by treatment with SAHA and DZNep, respectively. DYRK1A, CDK2, BMI-1 and Girdin, which are targets of miR-1246, miR-302a and miR-4448, were suppressed by treatment with SAHA and DZNep, leading to apoptosis, cell cycle arrest and reduced migration of AGS and HepG2 cells. 1596 miR-302a hsa-miR-302a-5p,hsa-miR-302a-3p MIMAT0000683,MIMAT0000684 miRNA CDK2 apoptosis down Homo sapiens AGS/HepG2 cell 24861464 9606 1017 CDKN2|p33(CDK2) HGNC:1771|MIM:116953|Ensembl:ENSG00000123374|HPRD:00310|Vega:OTTHUMG00000170575 12 12q13 cyclin-dependent kinase 2 protein-coding cyclin-dependent kinase 2 MiR-302a and miR-4448 were markedly upregulated by treatment with SAHA and DZNep, respectively. DYRK1A, CDK2, BMI-1 and Girdin, which are targets of miR-1246, miR-302a and miR-4448, were suppressed by treatment with SAHA and DZNep, leading to apoptosis, cell cycle arrest and reduced migration of AGS and HepG2 cells. 1597 miR-302a hsa-miR-302a-5p,hsa-miR-302a-3p MIMAT0000683,MIMAT0000684 miRNA DYRK1A apoptosis down Homo sapiens AGS/HepG2 cell 24861464 9606 1859 DYRK|DYRK1|HP86|MNB|MNBH|MRD7 HGNC:3091|MIM:600855|Ensembl:ENSG00000157540|HPRD:09018|Vega:OTTHUMG00000086657 21 21q22.13 dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A protein-coding dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A MiR-302a and miR-4448 were markedly upregulated by treatment with SAHA and DZNep, respectively. DYRK1A, CDK2, BMI-1 and Girdin, which are targets of miR-1246, miR-302a and miR-4448, were suppressed by treatment with SAHA and DZNep, leading to apoptosis, cell cycle arrest and reduced migration of AGS and HepG2 cells. 1598 miR-302a hsa-miR-302a-5p,hsa-miR-302a-3p MIMAT0000683,MIMAT0000684 miRNA apoptosis Homo sapiens NT2 cell 23625774 9606 7157 TP53|BCC7|LFS1|TRP53 HGNC:11998|Ensembl:ENSG00000141510|HPRD:01859|MIM:191170|Vega:OTTHUMG00000162125 17 17p13.1 tumor protein p53 protein coding tumor protein p53 MiR-302a induced apoptosis was further enhanced by silencing of p53 in NT2 cells. p53 levels were inversely associated with the expression of Oct4, Sox2, and Nanog in response to cisplatin. Thus, targeting miR-302a may offer new therapeutic interventions in TGCT. 1599 miR-302b hsa-miR-302b-5p,hsa-miR-302b-3p MIMAT0000714,MIMAT0000715 miRNA AKT1 apoptosis up Homo sapiens osteosarcoma cell 23845851 9606 207 AKT|CWS6|PKB|PKB-ALPHA|PRKBA|RAC|RAC-ALPHA HGNC:391|MIM:164730|Ensembl:ENSG00000142208|HPRD:01261|Vega:OTTHUMG00000170795 14 14q32.32 v-akt murine thymoma viral oncogene homolog 1 protein-coding v-akt murine thymoma viral oncogene homolog 1 Notably, miR-302b, which is stably low-expressed in osteosarcoma, could be induced by the epirubicin. Furthermore, we find that miR-302b can inhibit the osteosarcoma cell proliferation, promote cell apoptosis and cell cycle arrest MiR-302b can activate caspase-3 and regulate the Akt/pAkt, Bcl-2, Bim expression to increase the cell apoptosis. Meanwhile, miR-302b also attenuates cyclin D1 and CDKs expression to induce cell cycle arrest. 1600 miR-302b hsa-miR-302b-5p,hsa-miR-302b-3p MIMAT0000714,MIMAT0000715 miRNA BCL2 apoptosis up Homo sapiens osteosarcoma cell 23845851 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 Notably, miR-302b, which is stably low-expressed in osteosarcoma, could be induced by the epirubicin. Furthermore, we find that miR-302b can inhibit the osteosarcoma cell proliferation, promote cell apoptosis and cell cycle arrest MiR-302b can activate caspase-3 and regulate the Akt/pAkt, Bcl-2, Bim expression to increase the cell apoptosis. Meanwhile, miR-302b also attenuates cyclin D1 and CDKs expression to induce cell cycle arrest. 1601 miR-302b hsa-miR-302b-5p,hsa-miR-302b-3p MIMAT0000714,MIMAT0000715 miRNA BCL2L11 apoptosis up Homo sapiens osteosarcoma cell 23845851 9606 10018 BAM|BIM|BOD HGNC:994|MIM:603827|Ensembl:ENSG00000153094|HPRD:04828|Vega:OTTHUMG00000131256 2 2q13 BCL2-like 11 (apoptosis facilitator) protein-coding BCL2-like 11 (apoptosis facilitator) Notably, miR-302b, which is stably low-expressed in osteosarcoma, could be induced by the epirubicin. Furthermore, we find that miR-302b can inhibit the osteosarcoma cell proliferation, promote cell apoptosis and cell cycle arrest MiR-302b can activate caspase-3 and regulate the Akt/pAkt, Bcl-2, Bim expression to increase the cell apoptosis. Meanwhile, miR-302b also attenuates cyclin D1 and CDKs expression to induce cell cycle arrest. 1602 miR-302b hsa-miR-302b-5p,hsa-miR-302b-3p MIMAT0000714,MIMAT0000715 miRNA CASP3 apoptosis up Homo sapiens osteosarcoma cell 23845851 9606 836 CPP32|CPP32B|SCA-1 HGNC:1504|MIM:600636|Ensembl:ENSG00000164305|HPRD:02799|Vega:OTTHUMG00000133681 4 4q34 caspase 3, apoptosis-related cysteine peptidase protein-coding caspase 3, apoptosis-related cysteine peptidase Notably, miR-302b, which is stably low-expressed in osteosarcoma, could be induced by the epirubicin. Furthermore, we find that miR-302b can inhibit the osteosarcoma cell proliferation, promote cell apoptosis and cell cycle arrest MiR-302b can activate caspase-3 and regulate the Akt/pAkt, Bcl-2, Bim expression to increase the cell apoptosis. Meanwhile, miR-302b also attenuates cyclin D1 and CDKs expression to induce cell cycle arrest. 1603 miR-302b hsa-miR-302b-5p,hsa-miR-302b-3p MIMAT0000714,MIMAT0000715 miRNA CCND1 apoptosis down Homo sapiens osteosarcoma cell 23845851 9606 595 BCL1|D11S287E|PRAD1|U21B31 HGNC:1582|MIM:168461|Ensembl:ENSG00000110092|HPRD:01346|Vega:OTTHUMG00000167877 11 11q13 cyclin D1 protein-coding cyclin D1 Notably, miR-302b, which is stably low-expressed in osteosarcoma, could be induced by the epirubicin. Furthermore, we find that miR-302b can inhibit the osteosarcoma cell proliferation, promote cell apoptosis and cell cycle arrest MiR-302b can activate caspase-3 and regulate the Akt/pAkt, Bcl-2, Bim expression to increase the cell apoptosis. Meanwhile, miR-302b also attenuates cyclin D1 and CDKs expression to induce cell cycle arrest. 1604 miR-302b hsa-miR-302b-3p,hsa-miR-302b-5p MIMAT0000714,MIMAT0000715 miRNA CCND2 apoptosis down Homo sapiens SH-SY5Y cell 21878650 9606 894 KIAK0002 HGNC:1583|MIM:123833|Ensembl:ENSG00000118971|HPRD:00451|Vega:OTTHUMG00000168123 12 12p13 cyclin D2 protein-coding cyclin D2 Cotransfection studies with 3'-UTR of these genes and miRNA mimics have demonstrated that BCL2 is a direct target of miR-497 and that CCND2 is regulated negatively by either miR-302b or miR-497. Overexpression of either miR-497 or miR-302b reduced expression of their identified target genes and increased caspase 3-mediated apoptosis of SH-SY5Y cells. 1605 miR-302b hsa-miR-302b-5p,hsa-miR-302b-3p MIMAT0000714,MIMAT0000715 miRNA CDK7 apoptosis down Homo sapiens osteosarcoma cell 23845851 9606 1022 CAK1|CDKN7|HCAK|MO15|STK1|p39MO15 HGNC:1778|MIM:601955|Ensembl:ENSG00000134058|HPRD:15993|Vega:OTTHUMG00000099358 5 5q12.1 cyclin-dependent kinase 7 protein-coding cyclin-dependent kinase 7 Notably, miR-302b, which is stably low-expressed in osteosarcoma, could be induced by the epirubicin. Furthermore, we find that miR-302b can inhibit the osteosarcoma cell proliferation, promote cell apoptosis and cell cycle arrest MiR-302b can activate caspase-3 and regulate the Akt/pAkt, Bcl-2, Bim expression to increase the cell apoptosis. Meanwhile, miR-302b also attenuates cyclin D1 and CDKs expression to induce cell cycle arrest. 1606 miR-302b hsa-miR-302b-3p,hsa-miR-302b-5p MIMAT0000714,MIMAT0000715 miRNA E2F3 apoptosis down Homo sapiens glioma cell 25040912 9606 1871 E2F-3 HGNC:3115|MIM:600427|Ensembl:ENSG00000112242|HPRD:02693|Vega:OTTHUMG00000016389 6 6p22 E2F transcription factor 3 protein-coding E2F transcription factor 3 E2F3, an important transcriptional regulator of glioma proliferation, was validated to be a direct target gene of miR-302b. The miR-302b-reduced E2F3 levels were also identified to be associated with ATRA-mediated glioma cell death. These results emphasize that an ATRA-mediated miR-302b network may provide novel therapeutic strategies for glioblastoma therapy. 1607 miR-302b hsa-miR-302b-3p,hsa-miR-302b-5p MIMAT0000714,MIMAT0000715 miRNA ERBB4 apoptosis down Homo sapiens esophageal squamous cell 24438167 9606 2066 ALS19|HER4|p180erbB4 HGNC:3432|MIM:600543|Ensembl:ENSG00000178568|HPRD:02767|Vega:OTTHUMG00000133012 2 2q33.3-q34 v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4 protein-coding v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4 MiR-302b was significantly down-regulated and correlated with tumor differentiation and lymph node metastasis in ESCC. Univariate and multivariate analyses indicated that low miR-302b expression might be a poor prognostic factor. Further studies demonstrated that miR-302b post-transcriptionally down-regulated the expression of ErbB4 in vitro. Moreover, miR-302b inhibited proliferation by inducing apoptosis and repressed invasion in the ESCC cell lines. 1608 miR-302b hsa-miR-302b-3p,hsa-miR-302b-5p MIMAT0000714,MIMAT0000715 miRNA RUNX1 apoptosis down Homo sapiens ovarian cancer cell 25562167 9606 861 AML1|AML1-EVI-1|AMLCR1|CBFA2|EVI-1|PEBP2aB HGNC:10471|MIM:151385|Ensembl:ENSG00000159216|HPRD:01043|Vega:OTTHUMG00000086299 21 21q22.3 runt-related transcription factor 1 protein-coding runt-related transcription factor 1 Ectopic expression of miR-302b in EOC cells inhibited cell proliferation and colony formation, induced G0/G1 arrest, and promoted apoptosis. RUNX1 was identified as a direct target of miR-302b, and knockdown of RUNX1 inhibited cell growth in a manner similar to miR-302b overexpression, whereas introduction of a 3'UTR mutant of RUNX1 reversed the suppressive effect of miR-302b. 1609 miR-30a hsa-miR-30a-5p,hsa-miR-30a-3p MIMAT0000087,MIMAT0000088 miRNA BECN1 apoptosis down Homo sapiens chronic myeloid leukemia cells 22395361 9606 8678 ATG6|VPS30|beclin1 HGNC:1034|MIM:604378|Ensembl:ENSG00000126581|HPRD:05087|Vega:OTTHUMG00000180653 17 17q21 beclin 1, autophagy related protein-coding beclin 1, autophagy related miR-30a is a potent inhibitor of autophagy by downregulating Beclin 1 and ATG5 expression. 1610 miR-30a-5p hsa-miR-30a-5p MIMAT0000087 miRNA 7-Sep apoptosis down Homo sapiens glioblastoma cells 23383034 9606 989 CDC10|CDC3|NBLA02942|SEPT7A HGNC:1717|MIM:603151|HPRD:04398 7 7p14.2 septin 7 protein-coding septin 7 SEPT7 is a member of the septin family, which is a highly conserved subfamily of GTPases implicated in exocytosis, apoptosis, synaptogenesis, neurodegeneration and tumorigenesis. Our previous study has also demonstrated that SEPT7 expression is decreased in astrocytic gliomas with different grades and plays a tumor suppressor role. Additionaly, miR-30a-5p directly targeting SEPT7 was identified by the reporter gene assay. 1611 miR-30b hsa-miR-30b-5p,hsa-miR-30b-3p MIMAT0000420,MIMAT0004589 miRNA BCL2 apoptosis down Homo sapiens cardiomyocytes 24178239 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 Our results demonstrated that NF-¦ÊB positively regulated miR-30b expression in Ang II-induced cardiomyocytes apoptosis, and Bcl-2 was a direct target for miR-30b. 1612 miR-30b hsa-miR-30b-5p,hsa-miR-30b-3p MIMAT0000420,MIMAT0004589 miRNA CASP3 apoptosis down Homo sapiens tumor necrosis factor-related apoptosis-inducing ligand-resistant glioma cells 22964638 9606 836 CPP32|CPP32B|SCA-1 HGNC:1504|MIM:600636|Ensembl:ENSG00000164305|HPRD:02799|Vega:OTTHUMG00000133681 4 4q34 caspase 3, apoptosis-related cysteine peptidase protein-coding caspase 3, apoptosis-related cysteine peptidase We show that in TRAIL-resistant glioma cells, levels of different miRs are increased, and in particular, miR-30b/c and -21. We demonstrate that these miRs impair TRAIL-dependent apoptosis by inhibiting the expression of key functional proteins.Furthermore, we demonstrate that miR-30b/c and miR-21 target respectively the 3' untranslated region of caspase-3 and TAp63 mRNAs, and that those proteins mediate some of the effects of miR-30 and -21 on TRAIL resistance, even in human glioblastoma primary cells and in lung cancer cells. 1613 miR-30b hsa-miR-30b-5p,hsa-miR-30b-3p MIMAT0000420,MIMAT0004589 miRNA CASP3 apoptosis down Homo sapiens 23968872 9606 836 CPP32|CPP32B|SCA-1 HGNC:1504|MIM:600636|Ensembl:ENSG00000164305|HPRD:02799|Vega:OTTHUMG00000133681 4 4q34 caspase 3, apoptosis-related cysteine peptidase protein-coding caspase 3, apoptosis-related cysteine peptidase Transfection of a mimic of miRNA-30b led to decreases in alkaline phosphatase activity and expressions of Runx2, Smad1, and caspase-3. Furthermore, dual luciferase reporter assays confirmed that Runx2, Smad1, and caspase-3 are direct targets of miRNA-30b. 1614 miR-30b hsa-miR-30b-5p,hsa-miR-30b-3p MIMAT0000420,MIMAT0004589 miRNA RUNX2 apoptosis down Homo sapiens 23968872 9606 860 AML3|CBF-alpha-1|CBFA1|CCD|CCD1|CLCD|OSF-2|OSF2|PEA2aA|PEBP2aA HGNC:10472|MIM:600211|Ensembl:ENSG00000124813|HPRD:02566|Vega:OTTHUMG00000014774 6 6p21 runt-related transcription factor 2 protein-coding runt-related transcription factor 2 Transfection of a mimic of miRNA-30b led to decreases in alkaline phosphatase activity and expressions of Runx2, Smad1, and caspase-3. Furthermore, dual luciferase reporter assays confirmed that Runx2, Smad1, and caspase-3 are direct targets of miRNA-30b. 1615 miR-30b hsa-miR-30b-5p,hsa-miR-30b-3p MIMAT0000420,MIMAT0004589 miRNA SMAD1 apoptosis down Homo sapiens 23968872 9606 4086 BSP-1|BSP1|JV4-1|JV41|MADH1|MADR1 HGNC:6767|MIM:601595|Ensembl:ENSG00000170365|HPRD:03356|Vega:OTTHUMG00000161592 4 4q31 SMAD family member 1 protein-coding SMAD family member 1 Transfection of a mimic of miRNA-30b led to decreases in alkaline phosphatase activity and expressions of Runx2, Smad1, and caspase-3. Furthermore, dual luciferase reporter assays confirmed that Runx2, Smad1, and caspase-3 are direct targets of miRNA-30b. 1616 miR-30c hsa-miR-30c-5p,hsa-miR-30c-2-3p,hsa-miR-30c-1-3p MIMAT0000244,MIMAT0004550,MIMAT0004674 miRNA CASP3 apoptosis down Homo sapiens tumor necrosis factor-related apoptosis-inducing ligand-resistant glioma cells 22964638 9606 836 CPP32|CPP32B|SCA-1 HGNC:1504|MIM:600636|Ensembl:ENSG00000164305|HPRD:02799|Vega:OTTHUMG00000133681 4 4q34 caspase 3, apoptosis-related cysteine peptidase protein-coding caspase 3, apoptosis-related cysteine peptidase We show that in TRAIL-resistant glioma cells, levels of different miRs are increased, and in particular, miR-30b/c and -21. We demonstrate that these miRs impair TRAIL-dependent apoptosis by inhibiting the expression of key functional proteins.Furthermore, we demonstrate that miR-30b/c and miR-21 target respectively the 3' untranslated region of caspase-3 and TAp63 mRNAs, and that those proteins mediate some of the effects of miR-30 and -21 on TRAIL resistance, even in human glioblastoma primary cells and in lung cancer cells. 1617 miR-30d hsa-miR-30d-5p,hsa-miR-30d-3p MIMAT0000245,MIMAT0004551 miRNA MTDH apoptosis down Homo sapiens renal cell carcinoma cells 23416459 9606 92140 3D3|AEG-1|AEG1|LYRIC|LYRIC/3D3 HGNC:29608|MIM:610323|Ensembl:ENSG00000147649|HPRD:17459|Vega:OTTHUMG00000164692 8 8q22.1 metadherin protein-coding metadherin Functional analysis revealed that miR-30d overexpression suppresses cell proliferation and induces apoptosis in RCC cells, suggesting that miR-30d acts as a tumor suppressor. In searching for downstream targets of miR-30d, we found that miR-30d post-transcriptionally suppresses expression of the oncoprotein metadherin (MTDH) by destabilizing its mRNA. 1618 miR-31 hsa-miR-31-5p,hsa-miR-31-3p MIMAT0000089,MIMAT0004504 miRNA ABCB9 apoptosis down Homo sapiens lung 24099915 9606 23457 EST122234|TAPL HGNC:50|MIM:605453|Ensembl:ENSG00000150967|HPRD:09262|Vega:OTTHUMG00000168769 12 12q24 ATP-binding cassette, sub-family B (MDR/TAP), member 9 protein-coding ATP-binding cassette, sub-family B (MDR/TAP), member 9 Mechanistically, we showed that miR-31 confers DDP-induced apoptosis and that inhibition of ABCB9 is required for DDP resistance. The data demonstrate that miR-31 exerts an anti-apoptotic effect most likely through the inhibition of ABCB9 and thus provide a novel strategy involving the use of miR-31 as a potential target in NSCLC chemotherapy 1619 miR-31 hsa-miR-31-5p,hsa-miR-31-3p MIMAT0000089,MIMAT0004504 miRNA apoptosis Homo sapiens SEB-activated cells 25706292 9606 9606 Both compounds also down-regulated miR-31, which directly targets caspase-2 and influences apoptosis in SEB-activated cells. 1620 miR-3189 hsa-miR-3189-3p,hsa-miR-3189-5p MIMAT0015071,MIMAT0019217 miRNA CDKN1A apoptosis up Homo sapiens 25698447 9606 1026 CAP20|CDKN1|CIP1|MDA-6|P21|SDI1|WAF1|p21CIP1 HGNC:1784|MIM:116899|Ensembl:ENSG00000124762|HPRD:00298|Vega:OTTHUMG00000014603 6 6p21.2 cyclin-dependent kinase inhibitor 1A (p21, Cip1) protein-coding cyclin-dependent kinase inhibitor 1A (p21, Cip1) miR-3189 targets revealed that miR-3189 directly inhibits the expression of a large number of genes involved in cell cycle control and cell survival. In addition, miR-3189 downregulated the expression of multiple p53 inhibitors resulting in elevated p53 levels and upregulation of several p53 targets including p21 (CDKN1A), GADD45A and the miR-3189 host gene GDF15, suggesting miR-3189 auto-regulation. Surprisingly, miR-3189 overexpression in p53-/- cells upregulated a subset of p53-targets including GDF15, GADD45A, and NOXA, but not CDKN1A. Consistent with these results, overexpression of miR-3189 potently induced apoptosis and inhibited tumorigenicity in vivo in a p53-independent manner. 1621 miR-3189 hsa-miR-3189-3p,hsa-miR-3189-5p MIMAT0015071,MIMAT0019217 miRNA GADD45A apoptosis up Homo sapiens 25698447 9606 1647 DDIT1|GADD45 HGNC:4095|MIM:126335|Ensembl:ENSG00000116717|HPRD:00528|Vega:OTTHUMG00000009374 1 1p31.2 growth arrest and DNA-damage-inducible, alpha protein-coding growth arrest and DNA-damage-inducible, alpha miR-3189 targets revealed that miR-3189 directly inhibits the expression of a large number of genes involved in cell cycle control and cell survival. In addition, miR-3189 downregulated the expression of multiple p53 inhibitors resulting in elevated p53 levels and upregulation of several p53 targets including p21 (CDKN1A), GADD45A and the miR-3189 host gene GDF15, suggesting miR-3189 auto-regulation. Surprisingly, miR-3189 overexpression in p53-/- cells upregulated a subset of p53-targets including GDF15, GADD45A, and NOXA, but not CDKN1A. Consistent with these results, overexpression of miR-3189 potently induced apoptosis and inhibited tumorigenicity in vivo in a p53-independent manner. 1622 miR-3189 hsa-miR-3189-3p,hsa-miR-3189-5p MIMAT0015071,MIMAT0019217 miRNA GDF15 apoptosis up Homo sapiens 25698447 9606 9518 GDF-15|MIC-1|MIC1|NAG-1|PDF|PLAB|PTGFB HGNC:30142|MIM:605312|Ensembl:ENSG00000130513|HPRD:05608|Vega:OTTHUMG00000183360 19 19p13.11 growth differentiation factor 15 protein-coding growth differentiation factor 15 miR-3189 targets revealed that miR-3189 directly inhibits the expression of a large number of genes involved in cell cycle control and cell survival. In addition, miR-3189 downregulated the expression of multiple p53 inhibitors resulting in elevated p53 levels and upregulation of several p53 targets including p21 (CDKN1A), GADD45A and the miR-3189 host gene GDF15, suggesting miR-3189 auto-regulation. Surprisingly, miR-3189 overexpression in p53-/- cells upregulated a subset of p53-targets including GDF15, GADD45A, and NOXA, but not CDKN1A. Consistent with these results, overexpression of miR-3189 potently induced apoptosis and inhibited tumorigenicity in vivo in a p53-independent manner. 1623 miR-3189 hsa-miR-3189-3p,hsa-miR-3189-5p MIMAT0015071,MIMAT0019217 miRNA PMAIP1 apoptosis up Homo sapiens 25698447 9606 5366 APR|NOXA HGNC:9108|MIM:604959|Ensembl:ENSG00000141682|HPRD:12002|Vega:OTTHUMG00000132765 18 18q21.32 phorbol-12-myristate-13-acetate-induced protein 1 protein-coding phorbol-12-myristate-13-acetate-induced protein 1 miR-3189 targets revealed that miR-3189 directly inhibits the expression of a large number of genes involved in cell cycle control and cell survival. In addition, miR-3189 downregulated the expression of multiple p53 inhibitors resulting in elevated p53 levels and upregulation of several p53 targets including p21 (CDKN1A), GADD45A and the miR-3189 host gene GDF15, suggesting miR-3189 auto-regulation. Surprisingly, miR-3189 overexpression in p53-/- cells upregulated a subset of p53-targets including GDF15, GADD45A, and NOXA, but not CDKN1A. Consistent with these results, overexpression of miR-3189 potently induced apoptosis and inhibited tumorigenicity in vivo in a p53-independent manner. 1624 miR-3189 hsa-miR-3189-3p,hsa-miR-3189-5p MIMAT0015071,MIMAT0019217 miRNA TP53 apoptosis up Homo sapiens 25698447 9606 7157 BCC7|LFS1|P53|TRP53 HGNC:11998|MIM:191170|Ensembl:ENSG00000141510|HPRD:01859|Vega:OTTHUMG00000162125 17 17p13.1 tumor protein p53 protein-coding tumor protein p53 miR-3189 targets revealed that miR-3189 directly inhibits the expression of a large number of genes involved in cell cycle control and cell survival. In addition, miR-3189 downregulated the expression of multiple p53 inhibitors resulting in elevated p53 levels and upregulation of several p53 targets including p21 (CDKN1A), GADD45A and the miR-3189 host gene GDF15, suggesting miR-3189 auto-regulation. Surprisingly, miR-3189 overexpression in p53-/- cells upregulated a subset of p53-targets including GDF15, GADD45A, and NOXA, but not CDKN1A. Consistent with these results, overexpression of miR-3189 potently induced apoptosis and inhibited tumorigenicity in vivo in a p53-independent manner. 1625 miR-32 hsa-miR-32-5p,hsa-miR-32-3p MIMAT0000090,MIMAT0004505 miRNA BCL2L11 apoptosis down Homo sapiens prostate cancer cells 18676839 9606 10018 BAM|BIM|BOD HGNC:994|MIM:603827|Ensembl:ENSG00000153094|HPRD:04828|Vega:OTTHUMG00000131256 2 2q13 BCL2-like 11 (apoptosis facilitator) protein-coding BCL2-like 11 (apoptosis facilitator) bcl-2 interacting mediato In cell culture, E2F1 and p21/WAF1 were identified as targets of miR-106b, Bim of miR-32, and exportin-6 and protein tyrosine kinase 9 of miR-1. 1626 miR-32 hsa-miR-32-5p,hsa-miR-32-3p MIMAT0000090,MIMAT0004505 miRNA BTG2 apoptosis down Homo sapiens androgen-sensitive human prostate adenocarcinoma cells 22266859 9606 7832 PC3|TIS21 HGNC:1131|MIM:601597|Ensembl:ENSG00000159388|HPRD:03357|Vega:OTTHUMG00000035834 1 1q32 BTG family, member 2 protein-coding BTG family, member 2 miR-32 was demonstrated to reduce apoptosis, whereas miR-148a enhanced proliferation. 1627 miR-320 hsa-mir-320a,hsa-miR-320b,hsa-miR-320c MIMAT0000510,MIMAT0005792,MIMAT0005793 miRNA BCL2 apoptosis down Homo sapiens cholangiocarcinoma cells 19070389 9606 596 Bcl-2|PPP1R50 HGNC:990|MIM:151430|Ensembl:ENSG00000171791|HPRD:01045 18 18q21.3 B-cell CLL/lymphoma 2 protein-coding B-cell CLL/lymphoma 2 apoptosis regulator Bcl-2 The exogenous expression of mir-320 or mir-204 could negatively regulate Mcl-1 or Bcl-2 expression and facilitate chemotherapeutic drug-triggered apoptosis. 1628 miR-320 hsa-mir-320a,hsa-miR-320b,hsa-miR-320c MIMAT0000510,MIMAT0005792,MIMAT0005793 miRNA MCL1 apoptosis down Homo sapiens cholangiocarcinoma cells 19070389 9606 4170 BCL2L3|EAT|MCL1-ES|MCL1L|MCL1S|Mcl-1|TM|bcl2-L-3|mcl1/EAT HGNC:6943|MIM:159552|Ensembl:ENSG00000143384|HPRD:08870|Vega:OTTHUMG00000034867 1 1q21 myeloid cell leukemia 1 protein-coding myeloid cell leukemia 1 apoptosis regulator Bcl-2 The exogenous expression of mir-320 or mir-204 could negatively regulate Mcl-1 or Bcl-2 expression and facilitate chemotherapeutic drug-triggered apoptosis. 1629 miR-320a hsa-miR-320a MIMAT0000510 miRNA BANP apoptosis down Homo sapiens K563 cell 23876508 9606 54971 BEND1|SMAR1|SMARBP1 HGNC:13450|MIM:611564|Ensembl:ENSG00000172530|HPRD:16538|Vega:OTTHUMG00000137678 16 16q24 BTG3 associated nuclear protein protein-coding BTG3 associated nuclear protein miR-320a negatively regulates the expression of SMAR1 by directly binding to its 3'UTR. In response to mild DNA damage, miR-320a expression is decreased resulting in enhanced expression of SMAR1 protein, which in turn, reduces its targets, Bax and Puma inhibiting apoptosis. 1630 miR-320a hsa-miR-320a MIMAT0000510 miRNA BAX apoptosis down Homo sapiens K562 cell 23876508 9606 581 BCL2L4 HGNC:959|MIM:600040|Ensembl:ENSG00000087088|HPRD:02498|Vega:OTTHUMG00000160476 19 19q13.3-q13.4 BCL2-associated X protein protein-coding BCL2-associated X protein miR-320a negatively regulates the expression of SMAR1 by directly binding to its 3'UTR. In response to mild DNA damage, miR-320a expression is decreased resulting in enhanced expression of SMAR1 protein, which in turn, reduces its targets, Bax and Puma inhibiting apoptosis. 1631 miR-320a hsa-miR-320a MIMAT0000510 miRNA BBC3 apoptosis down Homo sapiens K563 cell 23876508 9606 27113 JFY-1|JFY1|PUMA HGNC:17868|MIM:605854|Ensembl:ENSG00000105327|HPRD:16165|Vega:OTTHUMG00000183489 19 19q13.3-q13.4 BCL2 binding component 3 protein-coding BCL2 binding component 3 miR-320a negatively regulates the expression of SMAR1 by directly binding to its 3'UTR. In response to mild DNA damage, miR-320a expression is decreased resulting in enhanced expression of SMAR1 protein, which in turn, reduces its targets, Bax and Puma inhibiting apoptosis. 1632 miR-320a hsa-miR-320a MIMAT0000510 miRNA SP1 apoptosis Homo sapiens vessel 25728840 9606 6667 - HGNC:11205|MIM:189906|Ensembl:ENSG00000185591|HPRD:01796|Vega:OTTHUMG00000170047 12 12q13.1 Sp1 transcription factor protein-coding Sp1 transcription factor Moreover, miR-320a expression inhibits human-derived endothelium cell proliferation and induces apoptosis. We also found that SP1 transcriptionally up-regulates hsa-miR-320a expression. Our observations indicate that miR-320a is a key regulator contributing to multiple aspects of atherogenesis. 1633 miR-322 miRNA TRAF3 apoptosis down Homo sapiens neural stem cell 25516495 9606 7187 CAP-1|CAP1|CD40bp|CRAF1|IIAE5|LAP1 HGNC:12033|MIM:601896|Ensembl:ENSG00000131323|HPRD:03539|Vega:OTTHUMG00000171902 14 14q32.32 TNF receptor-associated factor 3 protein-coding TNF receptor-associated factor 3 MiR-322 interacts with the 3'-UTR of TRAF3 and represses its translation. The miR-322-TRAF3 pathway is implicated in high glucose-induced caspase activation and apoptosis. 1634 miR-323-5p hsa-miR-323a-5p MIMAT0004696 miRNA IGF1R apoptosis Homo sapiens glioma cell 25556445 9606 3480 CD221|IGFIR|IGFR|JTK13 HGNC:5465|MIM:147370|Ensembl:ENSG00000140443|HPRD:00932|Vega:OTTHUMG00000149851 15 15q26.3 insulin-like growth factor 1 receptor protein-coding insulin-like growth factor 1 receptor Our findings showed that over-expression of miR-323-5p could promote apoptosis of U251 and inhibit the proliferation and migration of the glioma cells.In addition, dual-luciferase reporter assays were performed to determine the target site of miR-323-5p to IGF-1R 3'UTR. 1635 miR-326 hsa-miR-326 MIMAT0000756 miRNA HDAC3 apoptosis Homo sapiens 25138213 9606 8841 HD3|RPD3|RPD3-2 HGNC:4854|MIM:605166|Ensembl:ENSG00000171720|HPRD:08950|Vega:OTTHUMG00000129629 5 5q31 histone deacetylase 3 protein-coding histone deacetylase 3 HDAC3 showed a positive feedback loop with miRNAs such as miR-200b, miR-217, and miR-335. miR-200b, miR-217, and miR-335 negatively regulated the expression of miR-326 and the invasion and migration potential of cancer cells while enhancing the apoptotic effect of anti-cancer drugs. TargetScan analysis predicted miR-200b and miR-217 as negative regulators of cancer-associated gene, a cancer/testis antigen, which is known to regulate the response to anti-cancer drugs. HDAC3 and miR-326 acted upstream of the cancer-associated gene. Thus, we show that the miR-326-HDAC3 feedback loop can be employed as a target for the development of anti-cancer therapeutics. 1636 miR-326 hsa-miR-326 MIMAT0000756 miRNA NOB1 apoptosis down Homo sapiens glioma cell 23869222 9606 28987 ART-4|MST158|NOB1P|PSMD8BP1 HGNC:29540|MIM:613586|Ensembl:ENSG00000141101|HPRD:11395|Vega:OTTHUMG00000137576 16 16q22.3 NIN1/RPN12 binding protein 1 homolog (S. cerevisiae) protein-coding NIN1/RPN12 binding protein 1 homolog (S. cerevisiae) In the present study, the human Nin one binding protein (NOB1) was identified as a direct target of miR-326 and a potential oncogene in human glioma. Similar to NOB1 silencing by shRNA, overexpression of miR-326 in human glioma cell lines (A172 and U373) caused cell cycle arrest at the G1 phase, delayed cell proliferation and enhanced apoptosis. 1637 miR-326 hsa-miR-326 MIMAT0000756 miRNA PKM apoptosis down Homo sapiens glioma cell 20667897 9606 5315 CTHBP|HEL-S-30|OIP3|PK3|PKM2|TCB|THBP1 HGNC:9021|MIM:179050|Ensembl:ENSG00000067225|HPRD:01529|Vega:OTTHUMG00000172709 15 15q22 pyruvate kinase, muscle protein-coding pyruvate kinase, muscle Ectopic expression of miRNA-326 in glioma and glioma stem cells induced their apoptosis and reduced their metabolic activity. Strikingly, cells with high levels of PKM2 expressed lower levels of miR-326, suggestive of endogenous regulation of PKM2 by miR-326. 1638 miR-326 hsa-miR-326 MIMAT0000756 miRNA SMO apoptosis down Homo sapiens chronic myeloid leukemia CD34(+) cells 23341351 9606 6608 FZD11|Gx|SMOH HGNC:11119|MIM:601500|Ensembl:ENSG00000128602|HPRD:03294|Vega:OTTHUMG00000158421 7 7q32.3 smoothened, frizzled class receptor protein-coding smoothened, frizzled class receptor Additionally, overexpression of miR-326 led to downregulation of Smo, resulted in decreased cell proliferation and elevated rate of apoptosis in CML CD34(+) cells 1639 miR-328 hsa-miR-328-3p,hsa-miR-328-5p MIMAT0026486,MIMAT0000752 miRNA IGF1R apoptosis down Homo sapiens 22392900 9606 3480 CD221|IGFIR|IGFR|JTK13 HGNC:5465|MIM:147370|Ensembl:ENSG00000140443|HPRD:00932|Vega:OTTHUMG00000149851 15 15q26.3 insulin-like growth factor 1 receptor protein-coding insulin-like growth factor 1 receptor Furthermore, miRNA-328 suppressed the insulin growth factor 1 receptor, ultimately leading to apoptosis of pulmonary arterial smooth muscle cells. The posttranscriptional repression of L-type calcium channel-¦Á1C and insulin growth factor 1 receptor was further confirmed by luciferase reporter assay. These results showed that miRNA-328, an important protecting factor, plays a significant role in PA constriction and remodeling by regulating multiple gene targets in hypoxic pulmonary hypertension. 1640 miR-328 hsa-miR-328-3p,hsa-miR-328-5p MIMAT0026486,MIMAT0000752 miRNA apoptosis Homo sapiens biliary cell 19345069 9606 Quantitative PCR was employed to validate down-regulation of microRNA-122a (miR-122a) and miR-26a and the increased expression of miR-328 and miR-299-5p. The predicted targets of these miRNAs are known to affect cell proliferation, apoptosis, inflammation, oxidative stress, and metabolism. Our data are the first to demonstrate that PBC is characterized by altered expression of hepatic miRNA; however additional studies are required to demonstrate a causal link between those miRNA and the development of PBC. 1641 miR-330 hsa-miR-330-3p,hsa-miR-330-5p MIMAT0000751,MIMAT0004693 miRNA CDC42 apoptosis down