Downregulation of microRNA-129-2 by Hepatitis B Virus Promotes Cell Proliferation in Hepatocellular Carcinoma.

Abstract

Objective: MicroRNA-192-2 has been shown to have a role in the early diagnosis of hepatocellular carcinoma (HCC), but the relationship between microRNA-192-2 and hepatitis B virus (HBV) in HCC patients remains unclear.

Methods: Specimens were collected from 56 HCC patients diagnosed with HBV infection and 56 HCC patients without viral infection. HBV and miR-129-2 levels in HCC tissues, adjacent tissues, and cell lines were analyzed by RT‒PCR. miR-129-2 mimics were transfected to induce the overexpression of miR-129-2 and cell function was assessed by a wound healing test. Tumor formation experiments in nude mice were conducted to validate tumor proliferation.

Results: In HCC patients, miR-192-2 was significantly downregulated in tumor tissues compared to adjacent tissues. Notably, miR-192-2 level was even lower in HCC patients with HBV-infection than those without the viral infection. Moreover, there was a negative correlation between miR-192-2 and HBV levels. Regardless of HBV infection, patients with low miR-192-2 levels had poorer prognosis than those with high miR-192-2 levels. HBV infection suppressed miR-192-2 expression in HCC cell lines. Furthermore, overexpression of miR-192-2 significantly inhibited cell proliferation both in vitro and in vivo in the HBV-infected group.

Conclusion: Our study revealed that the expression of miR-192-2, a crucial tumor suppressor gene, was suppressed by the presence of HBV.