差异表达基因microRNA结合位点遗传变异与中国人乳腺癌发病机制的研究

项目名称： 差异表达基因microRNA结合位点遗传变异与中国人乳腺癌发病机制的研究

项目编号： No.81202109

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： 袁芃

作者单位： 中国医学科学院肿瘤医院

项目金额： 23万元

中文摘要： 乳腺癌是严重威胁女性健康的最常见肿瘤之一，肿瘤组织与正常组织差异表达基因在肿瘤的发生发展中起重要作用。microRNA（miRNA）参与细胞增殖、分化、凋亡等一系列生理功能，位于miRNA结合位点3'非翻译区的单核苷酸多态（single nucleotide polymorphism, SNP）可能通过改变差异表达基因与miRNA的结合而影响基因表达，从而与个体的肿瘤易感性相关。本课题组已通过数据库挖掘出乳腺癌中表达差异最显著的7个基因（包括BRCA1、BCAH1、KRAS等），并完成了对上述乳腺癌差异表达基因3'非翻译区中符合一定频率标准的8个SNP位点的基因分型，初步筛选出出2个与乳腺癌发病显著相关的SNP。本研究拟继续针对这两个SNP开展大样本量的病例-对照研究进行验证，并采用一系列生物化学和分子生物学实验，研究此遗传变异的生物学功能，进而为探索乳腺癌发生发展的分子机制和

中文关键词： 三阴性乳腺癌；FABP4；3`非翻译区；基因变异；预后

英文摘要： Breast Cancer ranked as a serious threat to women's health is one of the most common cancer in females. The differentially expressed genes of tumor and normal tissues play an important role in the occuring and development of the breast cancer. MicroRNA participates in the cell proliferation, differentiation, apoptosis and a series of physiological processes. The single nucleotide polymorphisms(SNPs) located in the miRNA binding sites' 3' untranslated region may affect the genes' expression by changing the combination between miRNA and the differentially expressed genes, and then be related to the individuals' tumor susceptibility. Our group has found the 7 (including BRCA1、BCAH1、KRAS and so on) most significant difference genes which were differentially expressed in breast cancer through the databases. We have also completed the genotying of the eight SNPs which meet the certain frequency standards and located in the 3' untranslated region of these differentially expressed genes and then initially obtained 2 SNPs that may be related to the breast cancer susceptibility. This study intends to continue to carry out a large sample size case-control study to verify these two SNPs and conduct a series of biochemistry and molecular biology experiments to research the biological functions of these genetic variations, th

英文关键词： triple-negative breast cancer；FABP4；3`UTR；genetic variant；prognosis