乙肝表面抗原（HBsAg）转基因小鼠可自发形成肝癌，但机制不明。我们研究证实：①人肝癌组织中Bmi1表达升高并与HBsAg表达呈正相关；②HBsAg可以促进肝癌细胞Bmi1表达和体内成瘤能力；③稳定上调Bmi1可诱导成体肝干细胞恶性转化为肝癌；④HBsAg阳性肝癌中，LncRNA-UHCC1表达显著升高且可靶向调控Bmi1。已知Bmi1在干细胞恶性转化中起关键作用。据此我们假设：HBsAg通过LncRNA-UHCC1激活Bmi1诱导成体肝干细胞恶性转化为肝癌。本项目拟在前期研究基础上阐明：稳定上调HBsAg能否调控LncRNA-UHCC1的表达并诱导肝干细胞癌变；LncRNA-UHCC1在肝干细胞恶性转化和HBsAg转基因小鼠肝癌形成中的作用；HBsAg调控LncRNA-UHCC1及其下游基因的分子机制。本课题旨在揭示HBsAg调控肝干细胞恶性转化的作用与机制，为肝癌靶向治疗提供实验依据。

It has been reported that Hepatocellular carcinoma (HCC) develops more frequently among hepatitis B surface antigen (HBsAg) transgenic mice, but the mechanism is unknown. We previously reported that: (1) the expression of Bmi1 was up-regulated and positively correlated with the expression of HBsAg in human HCC tissues; (2) HBsAg promotes the expression of Bmi1 and tumorigenicity of HCC cells; (3) Dysregulation of Bmi1 promotes malignant transformation of hepatic progenitor cells; (4)The expression of LncRNA-UHCC1 increased significantly in HBsAg-positive HCC and could target-regulate Bmi1.It is known that Bmi1 plays a key role in malignant transformation of stem cells. Given the above, we assumed that HBsAg could promote malignant transformation of hepatic progenitor cells into HCC by activating Bmi1 through LncRNA-UHCC1. The aim of this project is to clarify whether the up-regulation of HBsAg can regulate the expression of LncRNA-UHCC1 and induce the carcinogenesis of hepatic progenitor cells, the role of LncRNA-UHCC1 in the malignant transformation of hepatic progenitor cells and the formation of HCC in HBsAg transgenic mice. The molecular mechanism of HBsAg regulates the expression of LncRNA-UHCC1 and its downstream genes. The aim of this study is to reveal the role and mechanism of HBsAg in regulating malignant transformation of hepatic progenitor cells, and to provide experimental evidence for targeted therapy of HCC.