Study On Mechanisms Of MiR-29c To HBV Relative HCC

Objective:MicroRNAs (miRNAs) are a class of non-coding, single-stranded RNA molecules containing19to25nucleotides (nt). miRNAs play important roles at the post-transcriptional level by imperfect base-pairing with3’-untranslated regions (3’-UTR) of target mRNAs. miRNAs were found to be key regulators in a variety of biological processes, including cell cycle, cell differentiation, proliferation and apoptosis. A growing amount of evidence has indicated that miRNAs are extensively involved in the pathogenesis of many different human cancers. Recent studies have revealed that microRNA-29c (miR-29c) is involved in a variety of biological processes including carcinogenesis. The role of miR-29c remains largely unknown in Hepatitis B Virus (HBV) induced hepatocellular carcinoma (HCC).Methods:miR-29c expression analysis by qRT-PCR; Bioinformatic analysis of miR-29c target genes; RT-PCR for TNFAIP3; Construction of miR-29c expression plasmid; Transfection; Luciferase reporter assay; Western blot analysis; HBsAg and HBeAg assay; HBV-DNA assay; Apoptosis assay; Cell proliferation assay; Statistical analysis.Results:Here we report that miR-29c was significantly down-regulated in both HBV-related HCC cell lines as well as in clinical tissues compared with their corresponding controls. Tumor Necrosis Factor Alpha-Induced Protein3, a key regulator in inflammation and immunity, was found to be reversely correlated with miR-29c level and was identified as a target gene of miR-29c. Overexpression of miR-29c in HepG2.2.15cells effectively suppressed TNFAIP3expression and HBV DNA replication, as well as inhibited the cell proliferation and induced apoptosis.Conclusion:We conclude that miR-29c may play important roles as a tumor suppressive microRNA in the development and progression of HBV-related HCC by targeting TNFAIP3. Thus miR-29c and TNFAIP3represent key diagnostic markers and potential therapeutic targets for the prevention and treatment of HBV infection.