title: Down-regulation of miR-517a and miR-517c promotes proliferation of hepatocellular carcinoma cells via targeting Pyk2.
abstract: Growing evidence indicates that some tumor suppressive miRNAs are subject to epigenetic modifications during carcinogenesis. Here, we found that a large miRNA cluster of C19MC was upregulated in HCC cells after combined treatment with DNA methylation inhibitor and histone deacetylase inhibitor. MiR-517a and miR-517c were strikingly different from the remaining 41 miRNAs in C19MC. Ectopic expression of MiR-517a and miR-517c inhibited cell proliferation by blocking G2/M transition, whereas down-regulation of miR-517a and miR-517c facilitated cell growth. We further showed Pyk2 is a target of miR-517a and miR-517c and both the miRNAs are downregulated in HCC samples. These data collectively suggest that down-regulation of both miR-517a and miR-517c contribute to HCC development through regulating Pyk2.
authors.affiliation: Shanghai Institute of Digestive Surgery, Rui-Jin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui-Jin II Road, Shanghai 200025, China.
authors.forename: Rui-Fang
authors.initials: RF
authors.lastname: Liu
authors.forename: Xiao
authors.initials: X
authors.lastname: Xu
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Qian-Lan
authors.initials: QL
authors.lastname: Fei
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.forename: Yan-Dong
authors.initials: YD
authors.lastname: Li
authors.forename: Ze-Guang
authors.initials: ZG
authors.lastname: Han
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D015536:Down-Regulation; D051418:Focal Adhesion Kinase 2 / Q000235:genetics* / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D059467:Transcriptome
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C546349:MIRN517 microRNA, human; D035683:MicroRNAs; C012589:trichostatin A; D000077209:Decitabine; D015254:DNA Modification Methylases; D051418:Focal Adhesion Kinase 2; D001374:Azacitidine