LncRNA-ENST00000456816通过MAPK9/HIF-2α途径调控肾细胞癌发生发展的分子机制

Long noncoding RNAs (lncRNAs) have been documented as playing critical role in the development and progression of human cancers including renal cell carcinoma (RCC). Our previous study identified a novel lncRNA ENST00000456816 which was exclusively overexpressed in RCC and correlated with cancer progression and worse survival of RCC patients. A series of in vitro and in vivo experiments validated that ENST00000456816 could act as an oncogenic transcript. Further dual luciferase reporter gene experiments implied that ENST00000456816 activated the expression of hypoxia inducing factor 2 alpha (HIF-2α). Furthermore, RNA pull-down assay and subsequent RNA immunoprecipitation identified MAPK9 as a RNA binding protein of ENST00000456816, and there was a significant expression and functional correlation between MAPK9 and HIF-2α. All these results contributed to the hypothesis that ENST00000456816 might regulate the HIF-2α pathway through its RNA binding protein MAPK9, thus participating in the carcinogenesis of RCC. This project aims to elaborate the molecular mechanisms that how ENST0000456816 affects pivotal HIF-2α pathway in RCC via interaction of MAPK9 and HIF-2α. This project has the potential to broaden and deepen our understanding of RCC-associated molecular events and provides promising diagnostic and therapeutic targets for RCC.

长链非编码RNA作为近年研究热点，在人类肿瘤发生发展中发挥重要调节功能。我们前期发现一种新的肾癌特异性高表达LncRNA ENST00000456816并发现其表达与肾癌的进展和患者预后密切相关，体内外实验证实了其在肾癌中起肿瘤促进作用。随后通过荧光素酶实验筛选验证ENST00000456816可影响HIF-2α转录活性，同时RNA pull-down及RIP筛选验证出其结合蛋白MAPK9，此外发现MAPK9与HIF-2α存在表达及功能相关。因此提出假说，ENST00000456816的表达升高可以导致MAPK9/ HIF-2α途径异常，从而促进肾癌的发生发展。本项目拟阐明ENST00000456816通过其结合蛋白MAPK9调节HIF-2α在肾癌发生发展中的分子机制，进一步加深对肾癌相关分子事件的认识，为肾癌提供诊疗靶点。

长链非编码RNA作为近年研究热点，在人类肿瘤发生发展中发挥重要调节功能。我们.发现一种新的肾癌特异性高表达LncRNA ENST00000456816并发现其表达与肾癌的进展和患者预.后密切相关，证实了其在肾癌中起肿瘤促进作用。通过荧光素酶实验筛选验证.ENST00000456816可影响HIF-2α转录活性，同时RNA pull-down及RIP筛选验证出其结合蛋白MA.PK9，此外发现MAPK9与HIF-2α存在表达及功能相关。表明ENST00000456816的表达.升高可以导致MAPK9/ HIF-2α途径异常，从而促进肾癌的发生发展。阐明ENST000004.56816通过其结合蛋白MAPK9调节HIF-2α在肾癌发生发展中的分子机制，进一步加深对肾癌相.关分子事件的认识，为肾癌提供诊疗靶点。