MicroRNA-34c targets TGFB-induced factor homeobox 2,represses cell proliferation and induces apoptosis in hepatitis B virus-related hepatocellular carcinoma

Abstract

MicroRNAs (miRs) are short, non-coding RNAs with post-transcriptional regulatory functions. Previous studies have demonstrated that miR-34c is involved in diverse biological processes, including carcinogenesis. The aim of the present study was to investigate the role of miR-34c and its target genes in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Expression levels of miR-34c and its predicted target genes were measured. The target genes were validated by a luciferase assay. The effects of miR-34c restoration were evaluated by the detection of HBV antigens, cell proliferation and apoptosis in vitro, in addition to the tumor growth in vivo. The data demonstrated that miR-34c was downregulated in HBV-associated HCC clinical tissues and HCC cell lines compared with their corresponding controls. transforming growth factor-β-induced factor homeobox 2 (TGIF2), a transcription factor repressing transforming growth factor-β (TGFβ) signaling, was observed to be upregulated and was identified as a target gene of miR-34c. The restoration of miR-34c in HepG2.2.15 cells suppressed TGIF2 expression, HBV replication and viral antigen synthesis; inhibited cell proliferation; and induced apoptosis. miR-34c also inhibited tumor growth in a mouse model. The present study indicates that miR-34c may act as a tumor suppressor by targeting TGIF2 during HBV-associated hepatocellular carcinogenesis. miR-34c and TGIF2 may represent key regulatory factors, diagnostic markers and therapeutic targets for the prevention and treatment of HBV-associated HCC.