Author(s)

Xuejing Lin^1,2*, Ziming Mao^1,3*, Qin Zhang¹, Lei Chen¹, Haihua Qian¹, Chunying Liu^1,2#, Changqing Su^1,2#

¹Department of Molecular Oncology, Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai, China.
²National Center for Liver Cancer, Navy Military Medical University, Shanghai, China.
³Department of Endocrinology, Shanghai Ninth People’s Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.

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.

Hepatitis B Virus (HBV), Hepatocellular Carcinoma (HCC), Protein Phosphatase 2 Regulatory Subunit B’ Alpha (PPP2R5A), Serine/Threonine Protein Phosphatase 2A (PP2A), Tumor Suppressor

Lin, X. , Mao, Z. , Zhang, Q. , Chen, L. , Qian, H. , Liu, C. and Su, C. (2021) HBV Infection Promotes the Occurrence and Development of Hepatocellular Carcinoma through Impairing the Inhibitory Effect of PPP2R5A on MAPK/AKT/WNT Signaling Pathway. Engineering, 13, 197-214. doi: 10.4236/eng.2021.134015.