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 noncoding 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 miR196a is involved in the regulation of the aberrant proliferation of HCVHCC cells. In the study, miRNA expression was detected by quantitative polymerase chain reaction analysis. An AdHCV 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 miR196a, and that overexpression of miR196a in the HepG2 and Huh7 HCC cell lines promoted cell proliferation by inducing the G1S transition. Furthermore, the present study demonstrated that forkhead box O1 (FOXO1) was directly regulated by miR196a, and was essential in mediating the biological effects of miR196a in HCC. The overexpression of FOXO1 markedly reversed the effect of miR196a in HCC cell proliferation. Taken together, the data obtained in the present study provided compelling evidence that elevated expression levels of miR196a by the HCV core protein can function as an oncomicroRNA during HCVinduced cell proliferation by downregulating the expression of FOXO1, indicating a potential novel therapeutic target for HCV-related HCC.