hsa-miR-129-5p负调节Warburg效应和抑制肝癌生长转移的分子机理研究

项目名称： hsa-miR-129-5p负调节Warburg效应和抑制肝癌生长转移的分子机理研究

项目编号： No.81472549

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： 李友军

作者单位： 武汉大学

项目金额： 78万元

中文摘要： 肝癌严重危害人民生命健康。c-Myc（Myc）癌基因病理激活参与肝癌发生发展。我们前期发现：Myc在肝癌组织过表达，对维持肝癌细胞恶性表型是必需的；Myc/miRNA功能反馈通路调节肝细胞癌变；miRBase全数据库内鉴定和证实新的Myc直接调节miRNAs;其中miR-129-5p是Myc直接调节miRNAs之一； miR-129-5p和其前体分子在肝癌组织表达显著下调；用获得和丢失性功能证实它具有抑癌功能：抑制肝癌细胞转化和Warburg效应；在裸鼠中显著抑制皮下和肝内接种的肿瘤生长，抑制尾静脉接种的肺部转移。本项目应用现代实验技术继续研究miR-129-5p的表达调控、成熟和调节靶基因，抑制Warburg效应、肿瘤生长和转移的作用分子机理；并进行靶向干预，阐明它在肝癌防治中的作用。这将揭示肝癌中Myc调控miR-129-5p信号通路和其作用机制，为防治肝癌提供理论基础和新策略。

中文关键词： 微小RNA；Myc癌基因；肿瘤抑制；肿瘤转移

英文摘要： Liver cancer seriously does harm to people's lives and health. The c-Myc (Myc) oncogene is pathologically activated which is involved in the development of liver cancer. We have previously found that: Myc is overexpressed in hepatocellular carcinoma(HCC)tissues and is essential for the maintenance of malignant phenotypes of liver cancer; The Myc / miRNA function feedback loop regulates hepatocarcinogenesis; miRNAs directly regulated by Myc were identified and confirmed using series of technologies in the miRBase database; miR -129-5p is one of direct targets regulated by Myc; miR-129-5p and its precursors were significantly reduced in HCC tissues; The tumor suppressor functions of miR-129-5p were confirmed with gain and loss of function: it significantly inhibited transformation and Warburg effect of hepatocellular carcinoma cells; it significantly inhibited tumor growth post subcutaneous injection and intrahepatic inoculation, inhibited lung metastasis post tail vein inoculation in nude mice. Using modern experimental techniques this project continues to study the expression regulation and maturation processing of the miR-129-5p; to study the molecular mechanism of inhibition of Warburgh effect, tumor growth and metastasis; to study its targeted intervention to clarify its roles and mechanisms in the prevention and treatment of liver cancer. This will reveal the Myc/miR-129-5p signaling pathways and its mechanisms in hepatocarcinogenesis. It will also provide theoretical basis and new strategies for the prevention and treatment of liver cancer.

英文关键词： microRNA;Myc;tumor suppression;metastasis