LncRNA与非小细胞肺癌（NSCLC）发生发展的研究报道甚少。我们前期工作表明：组蛋白甲基转移酶EZH2能调控lnc SPRY4-IT1表达； 且lnc SPRY4-IT1表达下调，与NSCLC患者TNM分期、淋巴结转移及预后差密切相关；体外实验证实lnc SPRY4-IT1可影响NSCLC细胞的迁移侵袭能力，其分子机制值得深入研究。文献表明lncRNA的转录亦受组蛋白修饰调控，且lncRNA可作为 ceRNA通过miRNA调控肿瘤进程。本课题组已证实lnc SPRY4-IT1能与miR-197/23a种子序列直接结合，据此提出假设：EZH2介导表观遗传学水平沉默lncRNA SPRY4-IT1的表达，减弱其调控miR-197/23a的功能，从而促进肿瘤侵袭转移。拟通过临床标本，ChIP、荧光素酶实验、裸鼠模型等方法证实上述假设，为NSCLC发病机制，临床诊断、治疗及预后提供新理论依据。

Multiple lines of evidences link dysregulations of long noncoding RNAs (lncRNAs) to diverse human diseases, especially cancers. The roles of lncRNAs in the carcinogenesis of non-small cell lung cancer (NSCLC), however, are far from being fully elucidated. Our previous work has shown that down-regulated lnc SPRY4-IT1 was obviously associated with advanced pathological stage,lymph-node metastasis, and shorter overall survival of NSCLC patients. Over-expression of lnc SPRY4-IT1 in NSCLC cells was demonstrated to decrease the cell proliferation, migration, invasion, while lead to the promotion of cell apoptosis in vitro. Meanwhile, we found that the histone H3 lysine 27 (H3K27) tri-methylating enzyme, Enhancer of zeste homolog 2 (EZH2) may mediate silencing expression of lnc SPRY4-IT1. Recent studies show that lncRNAs have typical histone modifications that are involved in cancer processes. Moreover, according to the ceRNA (competing endogenous RNA) hypothesis, lncRNAs may elicit their biological activity through their ability to act as endogenous sponges for miRNAs, and such activity could in turn affect the distribution of miRNAs on their targets, thereby affecting tumor development and progression. Here, the results of luciferase reporting experiments showed that lnc SPRY4-IT1 could directly bind to miR-197/23a seed sequence. Therefore, we suppose that lnc SPRY4-IT1 may be a crucial metastatic factor, and silenced by EZH2 mediated epigenetic regulation. It could play the ceRNA activity to regulate miR-197/miR-23a function, thus leading to the activation of tumor invasion and metastasis-related signaling pathways. We will identify the aboved hypothesis by use of clinical samples,Chromatin immunoprecipitation, luciferase reporter , a nude mouse model of lung metastasis and other techniques. This study will enrich the molecular mechanism of NSCLC invasion and metastasis, and provide a novel molecular target for diagnosis, treatment and prognosis of advanced NSCLC.