MHBSt167 induced autophagy promote cell proliferation and EMT by activating the immune response in L02 cells

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 (MHBSt167) was investigated into eukaryotic expression plasmid pcDNA3.1(-). MHBSt167 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 MHBSt167-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 MHBSt167 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 MHBSt167-induced acceleration of cell proliferation and the cell cycle was abolished by autophagy or NF-κB inhibitors. Conclusion: In summary, MHBSt167 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 MHBSt167 in contributing to carcinogenesis.