TGFβ信号通路基因microRNA结合区域遗传变异与结直肠癌易感性及其机制研究

项目名称： TGFβ信号通路基因microRNA结合区域遗传变异与结直肠癌易感性及其机制研究

项目编号： No.81201570

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： 顾冬英

作者单位： 南京医科大学

项目金额： 23万元

中文摘要： 结直肠癌的发生发展是环境和遗传因素共同作用的结果，且存在明显的个体易感性。目前全基因组关联研究（GWAS）发现TGFβ信号通路中多个基因的单核苷酸多态性（SNPs）与结直肠癌发病风险有关，同时研究表明微小RNA（microRNA）广泛参与了细胞的生长、分化和凋亡等生物学过程，提示其可能在结直肠癌中发挥重要作用。本研究拟通过生物信息学方法确定TGFβ通路基因microRNA结合区域的SNPs，采用临床病例－对照研究方法，探讨候选SNPs与结直肠癌发病风险的关系，分析评价基因型－临床表型及基因－环境的交互作用。同时采用一系列分子生物学方法进一步探讨SNPs对靶基因转录后翻译调控的影响，最终阐明TGFβ信号通路基因microRNA结合区域SNPs参与结直肠癌发生发展的可能生物学机制，为今后结直肠癌的个体化预防和治疗提供重要的理论依据。

中文关键词： 结直肠癌；微小RNA；TGFBR1基因；；

英文摘要： Colorectal cancer (CRC) is the results of multi-genes combined with environmental factors, which shows significant individual susceptibility. Genome-wide association study (GWAS) has suggested that many SNPs in the TGFβ pathway genes are associated with CRC risk. Furthermore, many studies reveal that microRNAs are involved in cell growth differentiation, and apoptosis, which may play an important role in CRC carcinogenesis. This study will identify the candidate SNPs in miRNAs targeting TGFβ pathway genes via bioinformatics, and investigate the association between these SNPs and the risk of CRC in a case-control study. In addtion, we will explore the association between the genotypes and clinical phenotypes of CRC and the gene-environment interaction. We will determine the potential mechanism of candidate SNPs on affecting the the post-transcriptional regulation of targeting genes by using a series of molecular biological methods. The results will contribute to clarify the important role of SNPs in miRNAs binding with TGFβ pathway genes in the development of CRC and provide evidence in practice of individual prevention and therapy of CRC.

英文关键词： Colorectal cancer；miRNA；TGFBR1；；