MHBSt Induced Autophagy Promote Cell Proliferation and EMT by Activating the Immune Response in L02 Cells

Overview

Journal Virol J

Publisher Biomed Central

Specialty Microbiology

Date 2022 Jun 27

PMID 35761331

Authors

Bin Cheng

Qiong Wang

Zhiqiang Wei

Yulin He

Ruiming Li

Guohua Liu

Shaobo Zeng

Zhongji Meng

Affiliations

Soon will be listed here.

Abstract

Background: Hepatitis B virus can induce hepatocellular carcinoma (HCC) by inducing a host immune response against infected hepatocytes. C-terminally truncated middle surface protein (MHBSt) has been reported to contribute to HCC through transcriptional activation in epidemiology studies, while the underlying mechanism of MHBSt-induced HCC is unknown.

Methods: In this study, a premature stop at codon 167 in MHBS (MHBSt) was investigated into eukaryotic expression plasmid pcDNA3.1(-). MHBSt expressed plasmid was transfected into the L02 cell line, cell proliferation was analyzed by CCK-8 and high-content screening assays, the cell cycle was analyzed by flow cytometry, and epithelial-to-mesenchymal transition and autophagy were analyzed by immunoblotting and immunofluorescence. NF-κB activation and the MHBSt-induced immune response were analyzed by immunoblotting and immunofluorescence. IFN-α, IFN-β and IL-1α expression were analyzed by qPCR. Autophagy inhibitors were used to analyze the relationship between the immune response and autophagy.

Results: The results showed that MHBSt promoted L02 cell proliferation, accelerated cell cycle progression from the S to G2 phase and promoted epithelial-to-mesenchymal transition through ER-stress, leading to autophagy and NF-κB activation and increased immune-related factor expression. The MHBSt-induced acceleration of cell proliferation and the cell cycle was abolished by autophagy or NF-κB inhibitors.

Conclusion: In summary, MHBSt could promote cell proliferation, accelerate cell cycle progression, induce EMT and activate autophagy through ER-stress to induce the host immune response, supporting a potential role of MHBSt in contributing to carcinogenesis.

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