长链非编码RNA MDC1-AS遗传变异与膀胱癌发病风险的机制研究

项目名称： 长链非编码RNA MDC1-AS遗传变异与膀胱癌发病风险的机制研究

项目编号： No.81502198

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张振声

作者单位： 中国人民解放军第二军医大学

项目金额： 18万元

中文摘要： 长链非编码 RNA（lncRNA）已证实与肿瘤发生密切相关，但其序列相关的遗传变异对膀胱癌发生的意义和机制尚不清楚。我们前期发现lncRNA MDC1-AS参与膀胱癌发生过程，其机制为通过其互补区反义结合MDC1 mRNA，增加其稳定性和表达。并发现MDC1-AS存在多个单核苷酸多态性（SNP）位点。由此我们提出假说：lncRNA MDC1-AS基因遗传变异与膀胱癌易感性显著关联，关联SNPs位点可通过影响MDC1基因参与膀胱癌的发生发展。本项目在前期研究基础上，拟通过病例-对照研究方法探讨lncRNA MDC1-AS基因的遗传变异与膀胱癌发病风险的关系；在此基础上，采用分子生物学方法，研究遗传变异对MDC1-AS及其靶基因MDC1的功能学影响和潜在的分子机制。希望通过本研究阐明MDC1-AS遗传变异与膀胱癌易感性的关系，为膀胱癌早期筛检及病因学研究提供新的靶点和理论依据。

中文关键词： 膀胱癌；非编码RNA；遗传变异

英文摘要： Long non-coding RNAs (lncRNAs) is functional non-coding RNAs longer than 200 nucleotides without protein-coding capability, and involved in the development and progression of cancer. The mechanism of genetic variation of lncRNAs promoting pathogenesis of bladder cancer is not clear.Our previous studies have found that expression of lncRNA MDC1-AS was significantly lower in bladder cancer tissues than that in normal tissues, and implicated in development of bladder cancer by modulating the function of the complementary gene MDC1. Different genetic variants(single nucleotide polymorphisms,SNPs) located on lncRNA MDC1-AS was also found.So we raise a hypothesis: the genetic variants located on lncRNA MDC1-AS was related with susceptibility of bladder cancer,and effect its function by regulating the expression of genes encoded its complementary strand, and consequently participated in the development of bladder cancer. We plan to investigate the relationship between SNPs at lncRNA MDC1-AS and risk for bladder cancer in a case-control study. Furthermore, we will explore the molecular mechanism between the functional SNPs and modulation of MDC1-AS. This study is hopefully to discover the the relationship between SNPs at lncRNA MDC1-AS and susceptibility of bladder cancer,and to provide a novel target and important theoretical support for early screening and etiology of bladder cancer.

英文关键词： bladder cancer;non-coding RNAs ;genetic variation