Hepatitis B Virus X Protein and Hepatocarcinogenesis

Shuaichen Liu, Samantha S Y Koh, Caroline G L Lee, Shuaichen Liu, Samantha S Y Koh, Caroline G L Lee

Abstract

Chronic hepatitis B virus (HBV) infection is one of the most associated factors in hepatocarcinogenesis. HBV is able to integrate into the host genome and encode the multi-functional hepatitis B virus x protein (HBx). Although the mechanism between HBx and carcinogenesis is still elusive, recent studies have shown that HBx was able to influence various signaling pathways, as well as epigenetic and genetic processes. This review will examine and summarize recent literature about HBx's role in these various processes.

Keywords: HBx protein; hepatocarcinogenesis; hepatocellular carcinoma.

Figures

Figure 1
Figure 1
Hepatitis B virus (HBV) genome map. The genome of HBV is a double-stranded DNA (3.2 kb), which contains four overlapping open reading frames (ORFs) coding for viral envelope (pre-S1/pre-S2/S) (blue arrow), core proteins (pre-C/C) (yellow arrow), viral polymerase (green arrow), and HBx protein (red arrow). The genome contains four promoters, two enhancer regions (Enh1, Enh2), and two direct repeats (DR1, DR2).
Figure 2
Figure 2
HBx and its mutifuntional roles in hepatocarcinogenesis. Each box represents processes that HBx may potentially play a role. The black arrows indicate up or downregulation of miRNAs. Abbreviations are as follow: DBH-AS1: DBH antisense RNA 1; HULC: highly upregulated in liver cancer; LINE: long interspersed nuclear element; Dreh: downregulated expression by HBx; IGF2: insulin-like growth factor-2; PCDH10: protocadherin 10; MTA1: metastasis-associated protein 1; mCGIs: hypermethylated intragenic CpG islands; IGFBP3: IGF binding protein 3; CDH1: E-cadherin gene; SIRT1: NAD-dependent deacetylase sirtuin-1; DR5 death receptor 5; Bcl-2: B-cell lymphoma 2; Mcl-1: myeloid cell leukemia-1; TFIIH: transcription factor IIH; BER: base excision repair; hOGG1: human 8-oxoguanine DNA glycosylase 1; hMYHa: human 8-oxoguanine DNA glycosylase 1(hOGG1) and DNA glycosylase a; NQO1: NAD(P)H: quinone oxidoreductase 1; ROS: reactive oxygen species; Foxo4: forkhead box class O 4.

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