长链非编码RNA（lncRNA）可作为竞争内源性RNA（ceRNA）与miRNA之间互相调控，从而参与肿瘤发生发展。课题组前期已发现膀胱癌中存在大量差异表达lncRNA及其遗传变异，而lncRNA发挥ceRNA作用时可能受到miRNA反应元件（MREs）结合区域单核苷酸多态性（SNPs）的影响。因此，本项目在前期的研究基础上，拟通过表达谱芯片和生物信息学确定膀胱癌差异lncRNA发挥ceRNA作用的MREs结合区域SNPs，利用病例-对照研究方法分析该区域SNPs与膀胱癌发病风险的关系；并分析基因-基因、基因-环境交互作用以及基因型与临床表型的关联性；同时运用一系列分子生物学方法，进一步探讨SNPs对lncRNA作为ceRNA竞争抑制miRNA调控靶基因的影响，阐明lncRNA-miRNA-靶基因的生物学调控机制，最终揭示lncRNA作为ceRNA在膀胱癌易感性的作用及其生物学机制。

Long non-coding RNA (lncRNA) can interact with the miRNA as a competing endogenous RNA (ceRNA), contributing to the occurrence and development of cancer. Our previous study has identified a series of differently expressed lncRNAs and genetic variant of lncRNA in bladder cancer. However, the function of ceRNA for lncRNA could be regulated by the SNPs in miRNA response elements (MREs). Hence, based on our previous results, we will identify the MREs for differently expressed lncRNA as well as SNPs in MREs using the lncRNA expression array and bioinformatics. We will perform a case-control study to investigate the association between SNPs in MREs and bladder cancer risk as well as the interactions on gene-gene, gene-environment, and genotypes and clinical phenotypes. Further using a series of molecular biology methods, we will explore the effect of SNPs involving in lncRNA acting as ceRNA, and elucidate the regulator mechanism of lncRNA-miRNA-target genes. The present study will reveal the biological mechanism of lncRNA acting as ceRNA associated with the risk of bladder cancer.