XRCC4M/miR-9在维持肝癌干细胞特性中的作用及相关机制研究

项目名称： XRCC4M/miR-9在维持肝癌干细胞特性中的作用及相关机制研究

项目编号： No.81472243

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 夏强

作者单位： 上海交通大学

项目金额： 68万元

中文摘要： 肝癌是一种严重危害国民健康的重大高发恶性肿瘤，课题组的前期研究发现DNA修复基因XRCC4 基因突变体(XRCC4M)促进肝癌的发生发展，但机制不清楚。本项目的预实验发现XRCC4M 明显下调肝癌细胞内小分子miR-9 的表达水平，并影响肝癌肿瘤干细胞表型，Ataxin 3(AT3)在以上过程中起重要作用，因此，本课题将以此为线索开展以下研究工作：深入解析XRCC4M/miR-9/AT3之间的信号调控关系，明确该调节机制在维持肝癌干细胞特性中的重要作用，并研究与分析它们在肝癌患者早期预警、早期诊断、和判断预后中的临床意义。以上研究将首次阐述XRCC4M/miR-9/AT3通路的调控机制以及该通路在维持肝癌干细胞特性中的作用，有助于进一步阐明肝癌干细胞在肝癌的发生和发展中的意义及分子机制，为肝癌的防治供新的重要的科学支持。

中文关键词： C09_肝和肝内胆管肿瘤；XRCC4M；miR-9；Ataxin；3；肝癌干细胞

英文摘要： Hepatocellular carcinoma (HCC) is a major malignant tumor endangering the human health seriously. Our previous studies have shown that the mutation of DNA repair gene XRCC4 (XRCC4M) develops the tumorigenesis of HCC, however, the corresponding mechanism is unclear. Through the prepare experiment, we found that the XRCC4M significantly down-regulated microRNA-9 (miR-9) expression in liver cancer cells and correlated with the phenotypes of liver cancer stem cells; whereas ataxin 3 (AT3) might play important role in this modification process. Based on aforementioned knowledge, the following experiments will be planned in this project: (1) deeply investigating the regulation relationship among XRCC4M, miR-9, and AT3; (2) clearing the role of this regulation mechanism in the maintaining characters of liver cancer stem cells; and (3) investigating and analyzing the clinic significance of XRCC4M/miR-9/AT3 signal pathway for the early warning, the early diagnosis, and the prognostic analysis of HCC. These researches would first elaborate the regulation mechanism of XRCC4M/miR-9/AT3 signal pathway and their role in the maintaining characters of liver cancer stem cells. This might help for us not only to elucidate the clinic significance of liver stem cells in the carcinogenesis of HCC and the corresponding molecular mechanism, but to provide new experimental data about HCC prevention and treatment.

英文关键词： C09_hepatic and intrahepatic bile duct tumors;XRCC4M;miR-9;Ataxin 3;liver cancer stem cell