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Review
. 2021 Apr 16;10(8):1715.
doi: 10.3390/jcm10081715.

Host Epigenetic Alterations and Hepatitis B Virus-Associated Hepatocellular Carcinoma

Mirjam B Zeisel  1 , Francesca Guerrieri  1 , Massimo Levrero  1   2
Affiliations
Review

Host Epigenetic Alterations and Hepatitis B Virus-Associated Hepatocellular Carcinoma

Mirjam B Zeisel et al. J Clin Med. .

Abstract

Hepatocellular carcinoma (HCC) is the most frequent primary malignancy of the liver and a leading cause of cancer-related deaths worldwide. Although much progress has been made in HCC drug development in recent years, treatment options remain limited. The major cause of HCC is chronic hepatitis B virus (HBV) infection. Despite the existence of a vaccine, more than 250 million individuals are chronically infected by HBV. Current antiviral therapies can repress viral replication but to date there is no cure for chronic hepatitis B. Of note, inhibition of viral replication reduces but does not eliminate the risk of HCC development. HBV contributes to liver carcinogenesis by direct and indirect effects. This review summarizes the current knowledge of HBV-induced host epigenetic alterations and their association with HCC, with an emphasis on the interactions between HBV proteins and the host cell epigenetic machinery leading to modulation of gene expression.

Keywords: HBx; epidrugs; epigenetic regulation; hepatitis B virus; hepatocellular carcinoma; virus–host interactions.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the writing of the manuscript, or in the decision to publish the review.

Figures

Figure 1
Figure 1
Schematic representation of epigenetic writers (i.e., histone methyl-transferases (HMTs), histone acetyl-transferases (HAT), DNA methyltransferases (DNMT)), readers (e.g., TD, CD, BRD proteins, MBP) and erasers (i.e., HDM, HDAC, TET). Ac: acetylation; CD: chromodomain-containing protein; DNMT: DNA methyltransferase; HAT: histone acetyltransferase; HDAC: histone deacetylase; HDM: histone demethylase; TF: transcription factor; MBP: methyl CpG binding protein; Me: methylation; TD: Tudor domain-containing proteins; TET: Ten-eleven translocation. Images were adapted from SMART (Servier Medical Art).
Figure 2
Figure 2
Schematic representation of alterations of epigenetic modifiers, chromatin modifications and DNA methylation during hepatocarcinogenesis. TSG: tumor suppressor gene.
Figure 3
Figure 3
Schematic illustration of host gene transcription modulation by HBx. Examples of HBx interactions with the host cell epigenetic machinery and their effects on host gene transcription are shown. A description of HBx/PRC2 target genes are detailed in [33]. Ac: acetylation; DNMT: DNA methyltransferases; HAT: histone acetyltransferase; HMT: histone methyltransferase; HBx: hepatitis B virus (HBV) protein x; HDAC: histone deacetylase; TF: transcription factor; Me: methylation.
See this image and copyright information in PMC

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