10.6084/M9.FIGSHARE.C.6231684.V1
Long Liu
Long
Liu
Hubei University of Medicine
Yanping Huang
Yanping
Huang
Hubei University of Medicine
Yanan Fu
Yanan
Fu
Hubei University of Medicine
Jingjing Rao
Jingjing
Rao
Hubei University of Medicine
Feng Zeng
Feng
Zeng
Hubei University of Medicine
Manshan Ji
Manshan
Ji
Hubei University of Medicine
Xiang Xu
Xiang
Xu
Hubei University of Medicine
Jianyong Zhu
Jianyong
Zhu
Hubei University of Medicine
Weixing Du
Weixing
Du
Hubei University of Medicine
Zhixin Liu
Zhixin
Liu
Hubei University of Medicine
Hepatitis B virus promotes hepatocellular carcinoma development by activating GP73 to repress the innate immune response
Abstract Background Hepatitis B virus (HBV) causes acute and chronic infection in the clinic. Hepatocellular carcinoma (HCC) is closely linked to HBV infection. Serum Golgi protein 73 (GP73) increases during HBV infection. However, the role of GP73 during HBV infection and the occurrence of HBV-related HCC is still poorly understood. Methods The underlying role of HBV-induced GP73 in regulating HCC development was investigated in this study. GP73 expression in HBV-related clinical HCC tissues and in HBV-infected hepatoma cells and primary human hepatocytes was evaluated by immunohistochemistry, ELISAs, Western blotting and quantitative real-time PCR (qRT-PCR) analysis. Tumorigenicity of GP73 overexpressed cells was detected by flow cytometry, qRT-PCR, xenograft nude mouse analyses and sphere formation assays. The effects of GP73 and HBV infection on host innate immune responses in hepatocytes were further investigated by Western blotting and qRT-PCR analysis. Results Initially, we confirmed that HBV-positive HCC tissues had significantly higher expression of GP73. Ectopic expression of the HBV gene could induce GP73 expression in primary human hepatocytes and hepatoma cells in vitro. In addition, we discovered that GP73 promotes HCC in both normal liver cells and hepatoma cells. We also found that ectopic expression of HBV genes increases GP73 expression, suppressing the host's innate immune responses in hepatocytes. Conclusions Our results demonstrate that HBV facilitates HCC development by activating GP73 to repress the host's innate immune response. This study adds to our understanding of the pathogenesis of HBV infection-induced HCC. The findings also provide preclinical support for GP73 as a potential HCC prevention or treatment target.
Immunology
figshare
2022
2022-10-05
2022-10-05
Collection
10.6084/m9.figshare.c.6231684
CC BY 4.0