DNA甲基化、组蛋白修饰调控非小细胞肺癌lncRNA MALAT1表达的分子机制研究

项目名称： DNA甲基化、组蛋白修饰调控非小细胞肺癌lncRNA MALAT1表达的分子机制研究

项目编号： No.81201645

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 郭锋杰

作者单位： 天津医科大学

项目金额： 23万元

中文摘要： 肺癌作为危害人类健康的重大疾病，机制尚未阐明。目前，lncRNA成为研究热点。lncRNA在肿瘤领域的研究主要集中在其表达水平对肿瘤发生发展的影响，而有关调控lncRNA表达机制的研究较少，肿瘤中lncRNA受表观遗传形式调控方面的研究在国内外尚未开展。MALAT1是第一个在肺癌中鉴定的功能性lncRNA，MALAT1促进非小细胞肺癌侵袭转移，课题组前期发现，MALAT1基因上游调控区存在DNA甲基化、组蛋白修饰和非小细胞肺癌MALAT1基因表达密切相关，结合国内外有关研究，提出Dnmt1、MeCP2、PRC2、MLL参与DNA甲基化和组蛋白修饰，导致MeCP2、YB-1、TDP-43结合状态改变，从而调控MALAT1基因表达的设想。因此，本课题拟以DNA甲基化和组蛋白修饰为切入点，基于表观遗传学的研究思路，以非小细胞肺癌为研究对象，证实上述设想，为非小细胞肺癌的治疗提供新思路、新靶点。

中文关键词： 非小细胞肺癌；长链非编码RNA；MALAT1；表观遗传；

英文摘要： Lung cancer is a serious disease harming human health.However,the mechanisms have not yet been elucidated. At present long non-coding RNA（lncRNA）has become a research focus. Research of lncRNA in tumor field mainly concentrated in the effect of expression level of MALAT1 on the tumorigenesis and development, but study regulating lncRNA expression is less. Study that lncRNA in tumor is regulated by epigenetic forms has been not yet carried out at home and abroad. MALAT1 is the first functional lncRNA that is identified in lung cancer. MALAT1 promotes the migration and metastasis of non-small cell lung cancer (NSCLC). Our previous results showed that DNA methylation and histone modification,which existed in upstream regulatory region of MALAT1 gene,is closely related to the expression of MALAT1. In combination with domestic and foreign research, we propose that Dnmt1,MeCP2,PRC2 and MLL anticipate the DNA methylation and histone modification which induce the binding model of MeCP2,YB-1 and TDP-43 to alter and then regulate the expression of MALAT1.Therefore, this project will confirm these assumptions and provide new ideas and targets for NSCLC treatment with DNA methylation and histone modifications as the starting point and with NSCLC as the object of research based on epigenetic research ideas.

英文关键词： non-small cell lung cancer；long non-coding RNA；MALAT1；epigenetics；