Epigenetic Modifications in HBV‐Related Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Hepatitis B virus (HBV) is the main pathogen for HCC development. HBV covalently closed circular DNA (cccDNA) forms extra-host chromatin-like minichromosomes in the nucleus of hepatocytes with host histones, non-histones, HBV X protein (HBx) and HBV core protein (HBc). Epigenetic alterations are dynamic and reversible, which regulate gene expression without altering the DNA sequence and play a pivotal role in the regulation of HCC onset and progression. The aim of this review is to elucidate the deregulation of epigenetic mechanisms involved in the pathogenesis of HBV-related HCC (HBV-HCC), including post-translational histone and non-histone modifications, DNA hypermethylation and hypomethylation, non-coding RNA modification on HBV cccDNA minichromosomes and host factors, effecting the replication/transcription of HBV cccDNA and transcription/translation of host genes, and thus HBV-HCC progression. It is expected that the epigenetic regulation perspective provides new ways for more in-depth development of therapeutic control of HBV-HCC.