MicroRNA-34b/c基因启动子区多态性及其甲基化与肾癌遗传易感性及其机制研究

项目名称： MicroRNA-34b/c基因启动子区多态性及其甲基化与肾癌遗传易感性及其机制研究

项目编号： No.81201571

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 秦超

作者单位： 南京医科大学

项目金额： 23万元

中文摘要： 肾癌是常见的泌尿系统肿瘤。有研究表明，miR34b/c因甲基化失活参与了肾癌的发生。位于基因启动子区CpG岛的多态性可以通过影响基因的启动子活性或者甲基化状态来调节基因的表达。我们的前期研究发现位于pri-miR-34b/c基因CpG岛的rs4938723T>C位点和肾癌的易感性明显相关；rs4938723CC基因型携带者的肾癌发病风险明显增高，且CC基因型组织中成熟miR34b/c水平较其他型明显降低。本课题在前期研究的基础上，拟采用各种功能学方法进一步研究：pri-miR-34b/c基因启动子区rs4938723T>C多态性对该基因转录活性及转录因子特异性结合亲和性以及对基因甲基化状态的影响。初步阐明miR34b/c参与肾癌发生的可能生物学机制，为今后肾癌的早期预防、诊断和治疗提供重要参考。

中文关键词： 单核苷酸多态性；遗传易感性；miR-34b/c；肾癌；

英文摘要： Renal cell cancer (RCC) is a common urinary tract tumor. It has been suggested that inactivation of miR-34b/c by CpG methylation is involved in RCC carcinogenesis. Genetic polymorphism in the CpG island can influence the gene methylation status. The pri-miR-34b/c rs4938723T>C polymorphism located in the CpG island of pri-miR-34b/c has been reported to influence the susceptibility of hepatocellular carcinoma. This project will investigate the influence of pri-miR-34b/c rs4938723T>C polymorphism on the susceptibility of RCC and the potentially biological mechanisms. The preliminary studies have found the rs4938723CC genotype was associated with increased RCC risk and lower level of mature miR-34b/c in para-tumor tissues. The project intends to further study the mechanism underlying the regulation of rs4938723T>C on the expression of pri-miR-34b/c and the association between this polymorphism and methylation status of pri-miR-34b/c. The results of the project may contribute to the efforts directed to a better understanding of development of RCC and provide important reference for the early prevention, diagnosis, and treatment of RCC.

英文关键词： single nucleotide polymorphism；genetic susceptibility；miR-34b/c；renal cell carcinoma；