Published online Aug 14, 2014. doi: 10.3748/wjg.v20.i30.10238
Revised: April 30, 2014
Accepted: May 25, 2014
Published online: August 14, 2014
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.
Core tip: The available evidence supports a well-defined for the hepatitis B virus-encoded X protein (HBx) protein in viral-induced hepatocellular carcinoma. The progression cell cycle, transactivation potential, compromised DNA repair, inhibition the tumor suppressor gene and senescence-related factors are few of the key pathways by which HBx is known to promote pathogenesis. The activation and inhibition of cellular calcium and tyrosine kinase signaling pathways are some of the other pathways modulated by HBx expression. Individually charged amino acids (K-130, V-131, D-120, 121) and or steches of amino acids (132-140) present in the carboxy-terminus of HBx protein seems to enhance the protein’s ability to deregulates cellular processes.