HBV前S1抗原下调肝细胞表面MHC-Ⅰ并促进肝癌产生  

PreS1 Antigen of HBV Down-Regulates MHC-Ⅰon the Surface of Hepatocytes and Promotes Hepatocarcinogenesis

作　　者：饶晶晶 曾凤 姬满山 徐祥 余春芳 杨靖 刘龙 刘志新 RAO Jing-jing;ZENG Feng;JI Man-shan;XU Xiang;YU Chun-fang;YANG Jing;LIU Long;LIU Zhi-xin(Department of Medical Microbiology,School of Basic Medical Sciences,Hubei University of Medicine,Shiyan 442000,China)

机构地区：[1]湖北医药学院基础医学院医学微生物教研室,十堰442000

出　　处：《四川大学学报（医学版）》2022年第2期285-290,共6页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金(No.81902066、No.82002149)资助。

摘　　要：目的探讨慢性乙型肝炎病毒(HBV)感染诱发肝癌所涉及的内在机制。方法对稳定过表达HBV前S1抗原(preS1)的L02、HepG2和Huh7细胞进行流式细胞术、实时荧光定量和裸鼠成瘤等实验来评估preS1在HBV相关性肝癌发生中的作用。结果preS1诱导细胞肿瘤干细胞(CSCs)相关因子和表面标志分子的表达上调,增强细胞的裸鼠成瘤能力;过表达preS1可以下调细胞表面组织相容性复合体Ⅰ(MHC-Ⅰ)的表达;在细胞培养过程中加入γ干扰素(IFN-γ)可以恢复细胞表面MHC-Ⅰ的表达,降低细胞的裸鼠成瘤能力。结论preS1是HBV的一个致癌因子,通过下调肝细胞表面MHC I促进肝癌产生。Objective To explore the internal mechanism of hepatocellular carcinoma(HCC)induced by chronic hepatitis B virus(HBV)infection.Methods L02,HepG2 and Huh7 cells stably overexpressing HBV preS1 antigen were analyzed by flow cytometry,qRT-PCR and tumorigenesis in nude mice to evaluate the effect of preS1 antigen in HBV-related hepatocarcinogenesis.Results Our results showed that the expression of cancer stem cell(CSCs)related factors and cell surface markers in preS1 overexpressing cells were up-regulated,and the tumorigenicity of these cells was enhanced in nude mice.In addition,preS1 overexpression could down-regulate the expression of major histocompatibility complexⅠ(MHC-Ⅰ).The expression of MHC-Ⅰon the cell surface could be restored by adding interferon gamma(IFN-γ)in the process of cell culturing and the tumorigenicity of cells in nude mice could thus be reduced.Conclusion Based on the above results,we believe that preS1 is a carcinogen of HBV and that it promotes the formation of liver cancer through down regulating MHC-Ⅰon the surface of hepatocytes.

关 键 词：乙型肝炎病毒 肝癌 HBV前S1抗原 组织相容性复合体Ⅰ Γ干扰素 

分 类 号：R735.7[医药卫生—肿瘤]