HBV Infection Promotes the Occurrence and Development of Hepatocellular Carcinoma through Impairing the Inhibitory Effect of PPP2R5A on MAPK/AKT/WNT Signaling Pathway

Xuejing Lin,Lei Chen,Changqing Su,Ziming Mao,Haihua Qian,Chunying Liu,Qin Zhang

doi:10.4236/eng.2021.134015

Abstract

Reversible phosphorylation and dephosphorylation play important roles in cell function and cell signal transduction. PPP2R5A (protein phosphatase 2 regulatory subunit B’ alpha) is responsible for specifically regulating the catalytic function, substrate specificity and intracellular localization of the tumor suppressor phosphatase PP2A (serine/threonine protein phosphatase 2A). Therefore, the abnormal expression and function of PPP2R5A may be related to canceration. The aim of this study was to reveal its role in the occurrence and development of hepatocellular carcinoma (HCC). It is hoped that the results of this study can provide guidance for the prevention and treatment of HCC. The results showed that PPP2R5A inhibited the proliferation and metastasis of HCC cells, and acted as a tumor suppressor in HCC cells, but it had no significant effect on cell cycle. Further research found that PPP2R5A exerted tumor suppressor efficacy by inhibiting the MAPK/AKT/WNT signaling pathway. Combined with analysis of clinical tissue samples and TCGA database, it was found that the expression of PPP2R5A in tumor tissues of Chinese HCC patients was down-regulated and significantly correlated with the progression-free survival (PFS) of HCC patients. On the contrary, PPP2R5A showed an up-regulation trend in HCC cases in TCGA database although its effect on PFS was the same with that in Chinese HCC patients. Hepatitis B virus (HBV) infection is the main pathogenic factor of HCC in China. It was found that HBV infection reduced the content of PPP2R5A in cells. It was concluded that HBV inhibited the initiation of the protective mechanism mediated by PPP2R5A, making the occurrence and progress of HCC more “unimpeded”. This conclusion will further reveal the role of PPP2R5A in HBV-induced and HBV-unrelated HCC, therefore, providing clues for the prevention and treatment of the two types of HCC, respectively.

Highlights

China has a high incidence of hepatocellular carcinoma (HCC), while the vast majority of HCC are associated with Hepatitis B virus (HBV) infection [1] [2] [3]
The results showed that PPP2R5A inhibited the proliferation and metastasis of HCC cells, and acted as a tumor suppressor in HCC cells, but it had no significant effect on cell cycle
Combined with analysis of clinical tissue samples and TCGA database, it was found that the expression of PPP2R5A in tumor tissues of Chinese HCC patients was down-regulated and significantly correlated with the progression-free survival (PFS) of HCC patients

Summary

Introduction

China has a high incidence of hepatocellular carcinoma (HCC), while the vast majority of HCC are associated with HBV infection [1] [2] [3]. Reversible phosphorylation and dephosphorylation play important roles in the maintenance of cell homeostasis and the regulation of cell functions. About 50% of the serine/threonine dephosphorylation activity within cells is regulated by the serine/threonine protein phosphatase 2A (PP2A). PP2A is the most abundant phosphatase in cells, and its expression accounts for 0.2% - 1% of the total cell protein [4] [5] [6] [7]. The expression level, substrate specificity, intracellular localization and enzyme activity of PP2A are closely related to cellular physiological state and pathological state. It is generally believed that PP2A is a tumor suppressor, which can negatively regulate cell division, inhibit protein synthesis and promote cell apoptosis, and is a potential target for tumor targeted therapy [8] [9]

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