长链非编码RNA (lncRNA)可能在肿瘤发生中起重要作用，但关键环节尚未阐明。本研究基于前期肺癌全基因组关联研究（GWAS）结果，拟利用生物信息学等方法筛选lncRNA基因单核苷酸多态性（SNP）；然后采用大样本人群病例对照研究方法探讨这些SNP对肺癌发生的危险度，得到与肺癌相关的SNP，在此基础上探讨相关的基因-基因和基因-环境在肺癌发生中的交互作用；最后对已验证确定的lncRNA及其SNP进行相关的生物学功能研究，探讨这些SNP对所在lncRNA折叠结构、表达及与微小RNA结合能力的影响，评价lncRNA对肺癌细胞系增殖、凋亡、细胞周期及细胞集落形成等恶性表型的影响，寻找并验证lncRNA特异性结合蛋白及调控的信号通路。旨在发现新的与肺癌发生相关的lncRNA及其SNP，揭示它们在致癌过程中的关键作用，研究结果对深入阐释肺癌发生发展的内在机制和遗传易感性有重要学术价值。

Long non-coding RNAs (lncRNAs) may play important roles in the development of cancer, however its key points are not clear. This project will identify lncRNAs and their single nucleotide polymorphisms (SNPs) based on previous genome wide association study (GWAS) results of lung cancer using systematic review and bioinformatic methods. The case-control study including large sample size population will be applied to study the relationship between lncRNA SNPs and lung cancer risks, as well as gene-gene and gene-environment interaction. For significantly associated SNPs, biological significance will be explored. The impact of SNPs on the expression, structure and combination with microRNAs of lncRNA will be explored by real-time PCR, dual luciferase reporter gene assay system and bioinformatic methods. The influence of lncRNAs on proliferation, apoptosis, cell cycle and colony formation of lung cancer cell will be studied. By using the lncRNA knockdown and overexpression, combined with RNA pull-down, immunoprecipitation, real-time PCR, Western Blot, siRNA interference, the study will demonstrate that lncRNAs interact with proteins and regulate signal pathways. This project aims to find new lncRNAs and their SNPs associated with the susceptibility of lung cancer as well as their key roles in the development of cancer, which are valuable in understanding the molecular mechanism of lung cancer development.