LincRNA H19与乳腺癌风险的关联及相关功能研究

项目名称： LincRNA H19与乳腺癌风险的关联及相关功能研究

项目编号： No.81473039

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： 宋丰举

作者单位： 天津医科大学

项目金额： 75万元

中文摘要： 乳腺癌严重危害女性健康。非编码RNA在恶性肿瘤发生发展中的作用日益凸显，基因间长链非编码RNA（lincRNA）是这一领域内继microRNA之后新的研究热点。全基因组关联研究提示lincRNA H19与白种人乳腺癌发病风险的关联。H19调控一个重要的印记基因网络，包括IGF2和IGF2R。H19序列中包含miR-675，它调控多个肿瘤相关基因，包括IGF1R，RB和SET8。H19可能通过这两种途径影响乳腺癌的发生发展。本项目在前期发现的基础上，通过3000对乳腺癌病例对照样本分析 H19及相关功能元件区域15个独立SNP与乳腺癌发病和预后的关联；通过功能实验研究H19和miR-675对下游基因的作用和对细胞活性的影响。研究结果将有助于发现新的乳腺癌发病和预后分子标志物；有助于明确H19在乳腺癌发生发展中的作用及相关机制；有助于深入了解lincRNA与microRNA在肿瘤中的共同作用。

中文关键词： 乳腺癌；分子流行病学；微小RNA；基因间非编码大RNA；肿瘤流行病学

英文摘要： Breast cancer is a huge burden for women's health. The role of non-coding RNA in the development and progression of breast cancer is becoming more and more evident. Long intergenic non-coding RNA (lincRNA) is a new hot spot in this field after microRNA. Genome-wide association study (GWAS) reported association between lincRNA H19 and breast cancer risk in Caucasians. LincRNA H19 regulates a network of imprinted genes, including IGF2 and IGF2R. miR-675 is located within H19 sequence and regulates several cancer related genes, including IGF1R, RB, and SET8. H19 may be involved in the development and progression of breast cancer through these two mechanisms. In this study, we conduct a large case-control study with 3000 paired breast cancer cases and controls to investigate the association between 15 SNPs in H19 sequence and related functional units and the risk and prognosis of breast cancer, based on previous findings. We also conduct a functional study to investigate the effect of H19 and miR-675 on related genes and cell function, in breast cancer cell lines and tissue samples. The aim of this study is to find new biomarkers for breast cancer risk and prognosis; to demonstrate the function and mechanism for H19 in the development and progression of breast cancer; and to illustrate the relationship between lincRNA and microRNA, and the interaction of the two in cancer.

英文关键词： Breast cancer;Molecular epidemiology;microRNA;LincRNA;Cancer epidemiology