肝癌发病率高，预后差。在我国，乙肝病毒（HBV）感染是导致肝癌发生的罪魁祸首。研究证实RNA的异常甲基化修饰如m1A参与多种肿瘤的恶性进展，包括肝癌。我们前期研究发现，m1A甲基化转移酶复合物TRMT6/61A在肝癌组织中表达上调，且其高表达与肝癌尤其是HBV相关肝癌患者的预后呈正相关。功能实验证实TRMT6/61A在肝癌中发挥促癌作用。进一步研究发现TRMT6/61A可促进HBV复制和HBx表达，下调ZHX的表达。有研究报道ZHX可通过多种机制抑制HBV复制。因此，我们推测TRMT6/61A可通过m1A修饰降低ZHX2的翻译效率，促进HBx表达和HBV复制，进而加速肝癌的恶性进展。本项目拟在此基础上通过一系列体内外实验明确TRMT6/61A在肝癌发生和发展中的生物学功能，阐明TRMT6/61A通过介导ZHX的m1A修饰促进HBV相关肝癌进展的分子机制，为肝癌的治疗提供新的靶点和思路。

Hepatocellular carcinoma (HCC) is one of the most common malignancies and has an extremely poor prognosis. Hepatitis B virus (HBV) infection is a major cause of HCC in China. There is evidence showing that aberrant RNA methylation modifications such as m1A are involved in carcinogenesis, including HCC. Our preliminary data showed that m1A methyltransferase complex TRMT6/61A were significantly upregulated in HCCs compared to control subjects, and increased expression of TRMT6/61A were strongly associated with poor patient prognosis. Functional studies demonstrated that TRMT6/61A play oncogenic roles in HCC tumorigenesis. Further studies revealed that TRMT6/61A promoted HBV replication and HBx expression, while downregulated ZHX2 expression. Considering that ZHX2 has been demonstrated to suppress HBV replication, thus we suppose that TRMT6/61A promotes HBV replication and HBx expression by inducing m1A modification of ZHX2 and subsequently inhibiting its mRNA translation, thereby accelerating malignant progression of HBV-related HCC. In this project, we aimed to determine the biological function of TRMT6/61A in HCC, and clarify the mechanism of TRMT6/61A promoting malignant progress of HBV-related HCC. This study will provide a potential target and new strategy for HCC treatment.