Role of p53 suppression in the pathogenesis of hepatocellular carcinoma

Abstract

In the world, hepatocellular carcinoma (HCC) is among the top 10 most prevalent malignancies. HCC formation has indeed been linked to numerous etiological factors, including alcohol usage, hepatitis viruses and liver cirrhosis. Among the most prevalent defects in a wide range of tumours, notably HCC, is the silencing of the p53 tumour suppressor gene. The control of the cell cycle and the preservation of gene function are both critically important functions of p53. In order to pinpoint the core mechanisms of HCC and find more efficient treatments, molecular research employing HCC tissues has been the main focus. Stimulated p53 triggers necessary reactions that achieve cell cycle arrest, genetic stability, DNA repair and the elimination of DNA-damaged cells’ responses to biological stressors (like oncogenes or DNA damage). To the contrary hand, the oncogene protein of the murine double minute 2 (MDM2) is a significant biological inhibitor of p53. MDM2 causes p53 protein degradation, which in turn adversely controls p53 function. Despite carrying wt-p53, the majority of HCCs show abnormalities in the p53-expressed apoptotic pathway. High p53 in-vivo expression might have two clinical impacts on HCC: (1) Increased levels of exogenous p53 protein cause tumour cells to undergo apoptosis by preventing cell growth through a number of biological pathways; and (2) Exogenous p53 makes HCC susceptible to various anticancer drugs. This review describes the functions and primary mechanisms of p53 in pathological mechanism, chemoresistance and therapeutic mechanisms of HCC.

Keywords: Hepatocellular carcinoma, p53, Tumour suppressor gene, Murine double minute 2, Chemoresistance

Core Tip: This review articles covers all the points related to p53 gene suppression in the pathogenesis of hepatocellular carcinoma. The review manuscript also includes information about tumour suppressor P53, pathogenesis of P53-associated hepatocellular carcinoma (HCC), role of P53 in mechanisms of hepatocarcinogenesis, roles of P53 in extrinsic factor-induced liver carcinogenesis, relationship between hepatitis C virus core protein and P53 in HCC, other mechanisms of progression to cirrhosis and HCC.