HCV core protein-induced upregulation of microRNA-196a promotes aberrant proliferation in hepatocellular carcinoma by targeting FOXO1

The hepatitis C virus (HCV) core protein is critical in the development of hepatocellular carcinoma (HCC). Investigations on HCC have previously focused on microRNAs, a class of small non-coding RNAs, which are crucial in cancer development and progression. The present study aimed to investigate whether microRNA (miR)-196a is aberrantly regulated by the HCV core protein, and whether miR-196a is involved in the regulation of the aberrant proliferation of HCV-HCC cells. In the study, miRNA expression was detected by quantitative polymerase chain reaction analysis. An Ad-HCV core adenovirus was constructed and cell proliferation was measured using a Cell Counting Kit-8 assay and a cell cycle assay following infection. The results of the present study demonstrated that the HCV core protein increased the expression of miR-196a, and that overexpression of miR-196a in the HepG2 and Huh-7 HCC cell lines promoted cell proliferation by inducing the G1-S transition. Furthermore, the present study demonstrated that forkhead box O1 (FOXO1) was directly regulated by miR-196a, and was essential in mediating the biological effects of miR-196a in HCC. The overexpression of FOXO1 markedly reversed the effect of miR-196a in HCC cell proliferation. Taken together, the data obtained in the present study provided compelling evidence that elevated expression levels of miR-196a by the HCV core protein can function as an onco-microRNA during HCV-induced cell proliferation by downregulating the expression of FOXO1, indicating a potential novel therapeutic target for HCV-related HCC.