长链非编码RNA（lncRNA）是一类长度超过200个核苷酸，且生物学功能丰富的一类非编码RNA，参与肿瘤的发生发展。目前认为lncRNA的遗传变异（以单核苷酸多态性SNPs为主）可影响lncRNA的表达及其转录调控。本课题组前期通过全基因组lncRNAs芯片表达谱筛选，发现在结直肠癌组织中差异表达的lncRNA-422与结直肠癌的发生密切相关，但其机制尚不完全清楚。本项目拟基于前期实验结果和最新研究进展，针对lncRNA-422的遗传变异，采用两阶段的病例-对照研究，探讨lncRNA-422的SNPs与结直肠癌发病风险和临床表型的关联性；并综合采用一系列细胞分子生物学方法，研究遗传变异对lncRNA-422表达和分子调控的作用，进一步阐明lncRNA-422在结直肠癌发生发展过程中的生物学机制。该项目的实施可为今后实现结直肠癌早期预防和预后判断提供参考。

Long non-coding RNAs (lncRNAs) are a set of functional RNAs with longer than 200 nucleotides and no protein-coding capability, which have been reported involved in tumorigenesis. It has been demonstrated that lncRNAs genetic variations, mainly referring to SNPs, could affect lncRNAs expression and its transcriptional regulation. In our previous study, we have performed a global lncRNAs expression profile on colorectal cancer tissues, and identified lncRNA-422 as a candidate lncRNA for its association with colorectal cancer development and progression; however, its biological mechanisms have not been yet clear. In this study, we plan to conduct a two-stage case-control study to evaluate the association between lncRNA-422 SNPs and colorectal cancer risk and outcome. We will use a series of cellular and molecular biology methods to explore the effect of genetic variants on lncRNA-422 expression and molecular mechanisms, so as to further elucidate the biological mechanisms of lncRNA-422 during colorectal cancer development and progress. The project will provide reference for the early protection and clinical prognosis evaluation of colorectal cancer.