Hepatitis B virus X protein mediated epigenetic alterations in the pathogenesis of hepatocellular carcinoma

Chronic hepatitis B virus (HBV) infection is a worldwide health problem. Hepatitis B virus X protein (HBx), a pleiotropic regulatory protein encoded by HBV, is necessary for the transcription of HBV covalently closed circular DNA (cccDNA) minichromosomes, and affects the epigenetic regulation of host cells. The epigenetic reprogramming of HBx on host cell genome is strongly involved in HBV-related HCC carcinogenesis. Here, we review the latest findings of the epigenetic regulation induced by HBx protein in hepatocellular carcinoma (HCC), including DNA methylation, histone modification and non-coding RNA expression. The influence of HBx on the epigenetic regulation of cccDNA is also summarized. In addition, preliminary studies of targeted drugs for epigenetic changes induced by HBx are also discussed. The exploration of epigenetic markers as potential targets will help to develop new prevention and/or treatment methods for HBx-related HCC.