Down-regulation of miR-517a and miR-517c promotes proliferation of hepatocellular carcinoma cells via targeting Pyk2

• Published in: Cancer letters Vol. 329; no. 2; pp. 164 - 173
• Main Authors: Liu, Rui-Fang, Xu, Xiao, Huang, Jian, Fei, Qian-Lan, Chen, Fei, Li, Yan-Dong, Han, Ze-Guang
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 28.02.2013; Elsevier Limited
• Subjects: 5-Aza-2′-deoxycytidine; analogs & derivatives; antagonists & inhibitors; Azacitidine; Azacitidine - analogs & derivatives; Azacitidine - pharmacology; Base Sequence; Breast cancer; carcinogenesis; Carcinoma, Hepatocellular; Carcinoma, Hepatocellular - enzymology; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Cell growth; Cell Line, Tumor; Cell Proliferation; DNA methylation; DNA Modification Methylases; DNA Modification Methylases - antagonists & inhibitors; Down-Regulation; enzymology; epigenetics; Focal Adhesion Kinase 2; Focal Adhesion Kinase 2 - genetics; Focal Adhesion Kinase 2 - metabolism; G2 Phase Cell Cycle Checkpoints; G2/M arrest; gene expression regulation; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; genetics; Hematology, Oncology and Palliative Medicine; Hepatocellular carcinoma; hepatoma; histone deacetylase; Histone Deacetylase Inhibitors; Histone Deacetylase Inhibitors - pharmacology; Humans; Hydroxamic Acids; Hydroxamic Acids - pharmacology; Kinases; Liver cancer; Liver Neoplasms; Liver Neoplasms - enzymology; Liver Neoplasms - genetics; Liver Neoplasms - pathology; metabolism; microRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; MicroRNAs - physiology; Multigene Family; Oligonucleotide Array Sequence Analysis; pathology; pharmacology; physiology; RNA Interference; Transcriptome; Trichostatin A; Cell proliferation; Hepatocellular carcinoma; 5-Aza-2′-deoxycytidine; Trichostatin A; G2/M arrest
• ISSN: 0304-3835; 1872-7980; 1872-7980
• DOI: 10.1016/j.canlet.2012.10.027

► Human microRNA microarray analysis was performed on 8 HCC cell lines treated by DNA demethylation agent and histone deacetylase inhibitor. ► The largest human miRNA gene cluster C19MC on chromosome 19 was triggered by these epigenetic modification agents. ► Functional screen of 43 miRNAs on C19MC revealed that both miR-517a and miR-517c can suppress HCC cell growth. ► Both miR-517a and miR-517c inhibited cell proliferation by blocking G2/M transition. ► PYK2 is a target of both miR-517a and miR-517c. 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.