HBV Infection Promotes The Occurrence and Development of Hepatocellular Carcinoma Through Impairing The Inhibitory Effect of PPP2R5A on MAPK/AKT/WNT Signaling Pathway
Abstract Background: Reversible phosphorylation and dephosphorylation play important roles in cell function and cell signal transduction. PPP2R5A is responsible for specifically regulating the catalytic function, substrate specificity and intracellular localization of the tumor suppressor phosphatase PP2A. Therefore, the abnormal expression and function of PPP2R5A may be related to the occurrence and development of tumors.Results: This study showed that PPP2R5A inhibited the proliferation and metastasis of hepatocellular carcinoma (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. HBV infection is the main pathogenic factor of HCC in China. It was found that hepatitis B virus (HBV) infection reduced the content of PPP2R5A in cells.Conclusions: 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.