lncRNA HOTAIR与MRTF-A协同促进肿瘤细胞迁移和侵袭的分子机制研究

项目名称： lncRNA HOTAIR与MRTF-A协同促进肿瘤细胞迁移和侵袭的分子机制研究

项目编号： No.31500622

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 郑鹏

作者单位： 武汉科技大学

项目金额： 21万元

中文摘要： 长链非编码RNA（lncRNA）具有复杂的生物学功能，如致癌作用和肿瘤转移。HOTAIR被认为是一种致癌型的lncRNA，在肿瘤的发生发展中起着重要作用。MRTF-A是血清效应因子（SRF）的强力辅助转录因子，可以促进肿瘤细胞迁移和侵袭。而HOTAIR与MRTF-A之间是否存在联系以及在肿瘤细胞转移过程中的调控关系都有待于深入研究。前期研究表明：lncRNA芯片证明MRTF-A可以通过SRF结合HOTAIR启动子区域的CArG box调控HOTAIR的转录；定量蛋白质组学证明HOTAIR参与调控MRTF-A表达；同时抑制HOTAIR与MRTF-A表达导致肿瘤细胞迁移和侵袭能力降低。本研究将进一步证明HOTAIR与MRTF-A在肿瘤细胞的转移过程中协同调控作用以及可能存在的正反馈机制。本项目的实施将阐述HOTAIR与MRT-A之间的具体调控机制，为肿瘤的防治和治疗提供理论基础，具有重大意义。

中文关键词： 长链非编码RNA；HOX基因的反义基因间RNA；协同作用；迁移；侵袭

英文摘要： Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides, involves in various biological processes such as carcinogenesis and metastasis. HOTAIR (HOX antisense intergenic RNA), a lncRNA overexpressed in most human cancers, has been recognized as an oncogenic lncRNA. MRTF-A (Myocardin-related transcription factors A) is a powerful co-transcription factor of serum response factor and can promoted the cells migration and invasion. However, the regulative relation between HOTAIR and MRTF-A with metastasis in cancer are subjected to in-depth study. Our previous studies have demonstrated that MRTF-A can regulate the transcription of HOTAIR by binding the CArG box in HOTAIR promoter region by lncRNA chip, and HOTAIR may induce the expression of MRTF-A by quantitative proteomics. The migration capacity and invasiveness were reduced, when inhibited the expression of HOTAIR and MRTF-A simultaneously. With a variety of molecular and cell biology method, this study will further investigate the mechanism of synergistically promoting cancer cell migration and invasion by lncRNA HOTAIR and MRTF-A in vivo and vitro. And there is a positive feed-back between them. The intensive functional study will be carry out to fully understand the functions and mechanism, and provide the theoretical basis for cancer prevention and therapies, which will be of great theoretical and practical significance.

英文关键词： long non-coding RNA;HOTAIR;synergistical;migration ;invasion