Hepatitis B virus, HBx mutants and their role in hepatocellular carcinoma - PubMed (original) (raw)

Review

Hepatitis B virus, HBx mutants and their role in hepatocellular carcinoma

Ashraf Ali et al. World J Gastroenterol. 2014.

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of death induced by cancer in the modern world and majority of the cases are related to chronic hepatitis B virus (HBV) infection. HBV-encoded X protein (HBx) is known to play a pivotal role in the pathogenesis of viral induced HCC. HBx is a multifunctional protein of 17 kDa which modulates several cellular processes by direct or indirect interaction with a repertoire of host factors resulting in HCC. HBX might interfere with several cellular processes such as oxidative stress, DNA repair, signal transduction, transcription, protein degradation, cell cycle progression and apoptosis. A number of reports have indicated that HBx is one of the most common viral ORFs that is often integrated into the host genome and its sequence variants play a crucial role in HCC. By mutational or deletion analysis it was shown that carboxy terminal of HBx has a likely role in protein-protein interactions, transcriptional transactivation, DNA repair, cell, signaling and pathogenesis of HCC. The accumulated evidence thus far suggests that it is difficult to understand the mechanistic nature of HBx associated HCC, and HBx mediated transcriptional transactivation and signaling pathways may be a major determinant. This article addresses the role of HBx in the development of HCC with particular emphasis on HBx mutants and their putative targets.

Keywords: Activating protein; Apoptosis; Epigenetics; Hepatitis B virus; Hepatocellular carcinoma; Mitogen activated protein kinase; Mutants; Transcription factors; Transforming growth factor; Tumor necrosis factor.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Schematic depicting the potential contributions of hepatitis B virus -encoded protein in different cellular processes. It influences the apoptosis, transcription, DNA repair and epigenetic changes as well as affecting transactivation mechanism. MAPK: Mitogen activated protein kinase; TGF: Transforming growth factor; IL: Interleukin; PKC: Protein kinase C; ATF: Activating transcription factor; NF-κB: Nuclear factor kappa B; ASPP: Apoptosis-stimulating protein of p53; ERK: Extracellular signal-regulated kinases; JNK: Janus kinase; HIF: Hypoxia-inducible factor.

References

    1. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;379:1245–1255. - PubMed
    1. Lupberger J, Hildt E. Hepatitis B virus-induced oncogenesis. World J Gastroenterol. 2007;13:74–81. - PMC - PubMed
    1. Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol. 2009;27:1485–1491. - PMC - PubMed
    1. Sun TT, Chu YY. Carcinogenesis and prevention strategy of liver cancer in areas of prevalence. J Cell Physiol Suppl. 1984;3:39–44. - PubMed
    1. Chen X, Dai B, Liu Z, Gao J, Ji Z, Guo J, Chen G, Deng Z, Shao Z. A novel B/C inter-genotype recombinant of hepatitis B virus identified in north-west China. J Gen Virol. 2014;95:153–155. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources