HBX suppresses PTEN to promote the malignant progression of hepatocellular carcinoma through mi-R155 activation

Introduction and objectives: Hepatocellular carcinoma (HCC) is one of the most common and fatal tumors in the world, ranking third in cancer-related mortality. Chronic HBV infection is one of the major risk factors for hepatocellular carcinoma in China, Korea, and Sub-Saharan Africa. The HBx protein encoded by the X gene of HBV is a broadly regulated protein involved in transcriptional activation, epigenetics, apoptosis, DNA repair, and other regulatory processes. This study aimed to investigate the mechanism of HBx regulation of miR-155 and PTEN (Phosphatase and tensin homolog deleted on chromosome ten) in HBV-HCC. Methods: Exosomal miR-155 quantity was analyzed by sampling serum exosomes of patients with hepatocellular carcinoma and normal subjects. The analysis was divided into different subgroups according to HBV positivity or negativity. At the cellular level, the biological roles of HBX, microRNA-155 and PUN on hepatocellular carcinoma cells and their regulatory relationships with each other were verified. Results: MicroRNA-155 and PUN expression in HBV-positive HCC liver cancer tissues were negatively correlated, and HBX and miR-155 expression were positively correlated; microRNA-155 could target and inhibit PTEN expression, thereby promoting hepatocellular carcinoma cell activity, inhibiting apoptosis, and promoting invasion and migration; HBX could upregulate microRNA-155 thereby inhibit PUN to promote malignant transformation of hepatocellular carcinoma. Conclusions: HBX could promote malignant transformation of hepatocellular carcinoma cells by upregulating microRNA-155 expression and thereby inhibiting the PTEN/PI3K-AKT pathway. Blocking miR-155 expression could attenuate the proliferation-promoting and invasive effects of HBX. (C) 2022 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U.

Automated summary

This study investigated the mechanism of HBx regulation of miR-155 and PTEN in HBV-HCC, revealing that miR-155 promotes hepatocellular carcinoma cell activity, inhibits apoptosis, and promotes invasion and migration. HBx can promote malignant transformation of hepatocellular carcinoma cells by upregulating miR-155.