CCND1基因rs9344位点多态性影响汉族女性宫颈癌易感性的机制研究

项目名称： CCND1基因rs9344位点多态性影响汉族女性宫颈癌易感性的机制研究

项目编号： No.81202047

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2

项目作者： 王宁

作者单位： 中国医科大学

项目金额： 23万元

中文摘要： 人乳头瘤病毒（HPV）感染是宫颈癌的首要病因。个体遗传易感性差异影响HPV感染后的恶性转化。细胞周期调控异常是宫颈上皮细胞恶性转化的重要环节。CCND1基因表达的cyclin D1是细胞周期调节关键蛋白。我们前期实验显示CCND1基因rs9344位点多态性影响汉族女性宫颈癌易感性，并通过蛋白亚型cyclin D1b的差异表达影响宫颈癌的个体易感性及宫颈癌的分化程度。由于cyclin D1与HPV-16 E7蛋白Rb结合位点的同源性，我们推测cyclin D1b的减少间接促进宫颈癌的发生，并可能导致其向低分化转化。本课题拟在体外采用基因转染、基因沉默、免疫共沉淀和报告基因等技术，结合体内实验了解cyclin D1b蛋白对HPV感染后宫颈癌发生发展及分化程度的影响，并随访预后。阐明rs9344位点不同基因型易感风险差异的机制，为宫颈癌遗传风险研究提供参考，为评价宫颈癌的易感风险和预后提供帮助。

中文关键词： 宫颈癌；单核苷酸多态性；CCND1；cyclin D1b；miR-195

英文摘要： Human papillomavirus (HPV) infection is the leading cause of cervical cancer. Individual genetic susceptibility differences affect the transformation after HPV infection. Abnormal cell cycle regulation is an important procedure for cervical cells transformation. Cyclin D1 expressed by CCND1 gene is a key protein regulating cell cycles. Our previous experiments showed that CCND1 gene rs9344 polymorphism influence cervical cancer susceptibility of Han women by different expression of subtype cyclin D1b protein, resulting in differences of susceptibility and differentiation. As HPV-16 E7 showed homology with the Rb-binding sites of cyclin D1, we hypothesize that the decline of cyclin D1b may promote the transformation indirectly and may facilitate the transformation into the poor level. This project intends to use in vitro gene transfection, gene silencing, co-immunoprecipitation and reporter gene technology, combined with in vivo experiments and follow-up to investigate the role of cyclin D1b protein in cervical cancer development, differentiation and its value of prognosis, to clarify the mechanism of the rs9344 genotypes different susceptibility, to provide an example for research of genetic risk of cervical cancer, and to help evaluating cervical cancer risk and prognosis.

英文关键词： cervical cancer；Single Nucleotide Polymorphism；CCND1；cyclin D1b；miR-195