长链非编码RNA RP11-436H11.5作为ceRNA调控BCL-W介导的肾癌侵袭转移的分子机制

The mechanism of invasion and metastasis of renal cell carcinoma mediated by BCL-W is not clear now. We found that lncRNA RP11-436H11.5 was highly expression in renal cell carcinoma and was positively correlated with the expression of BCL-W. The invasion and metastasis of renal cell carcinoma and the expression of BCL-W decreased when RP11-436H11.5 was transfected by silence plasmid. BCL-W was one of the targeted genes of miR-335 in renal cancer cell. We found that there was a binding site of miR-335 in RP11-436H11.5 by theoretical prediction, suggesting that RP11-436H11.5 could regulate BCL-W expression and influence invasion and metastasis of renal cell carcinoma as a ceRNA. Our project aims to analyze the relationship between invasion and metastasis of renal cell carcinoma mediated by RP11-436H11.5 and BCL-W. We also want to find the mechanism of action of RP11-436H11.5 as a ceRNA regulating BCL-W. Finally, we investigate the invasion and metastasis of renal cell carcinoma by RP11-436H11.5 regulating the activity of BCL-W through miR-335 intervention. The results of this study are expected to find a new target for reversal of invasion and metastasis of renal cell carcinoma. Further more, it could lay a theoretical and experimental foundation for the mechanism of genesis and development of renal cell carcinoma.

BCL-W介导肾癌侵袭转移，但其调控机制不清。申请者发现长链非编码RNA RP11-436H11.5在肾癌组织中高表达，并与BCL-W表达正相关；肾癌细胞株中转染RP11-436H11.5沉默质粒后；细胞侵袭转移能力下降，BCL-W表达降低；肾癌细胞中BCL-W是miR-335靶基因之一；理论预测RP11-436H11.5存在与miR-335结合位点，提示RP11-436H11.5可能作为ceRNA调控BCL-W表达及其介导的肾癌侵袭转移。本项目拟分析RP11-436H11.5介导的肾癌细胞侵袭和转移与BCL-W的相关性，明确RP11-436H11.5以ceRNA方式调控BCL-W表达作用机制，考察RP11-436H11.5通过miR-335调节BCL-W对肾癌细胞侵袭和转移的影响，为寻找肾癌侵袭转移形成与逆转的新靶点，进一步阐明肾癌发生发展机制奠定理论与实验基础。

BCL-W介导肾癌侵袭转移，但其调控机制不清。近来研究发现lncRNA在多种肿瘤中异常表达，并与肿瘤侵袭、转移及复发密切相关。本项目拟分析长链非编码RNA RP11-436H11.5介导的肾癌细胞侵袭和转移与BCL-W的相关性。本项目主要研究了：(1) lncRNA RP11-436H11.5调控BCL-W对肾癌侵袭和转移的影响；(2) lncRNA RP11-436H11.5以ceRNA方式调控BCL-W的作用机制；(3) lncRNA RP11-436H11.5通过miR-335调节BCL-W对肾癌侵袭和转移的影响。本项目研究发现lncRNA RP11-436H11.5在肾癌组织中较癌旁正常组织呈高表达。生存分析结果提示，lncRNA RP11-436H11.5高表达的肾癌患者，其预后较lncRNA RP11-436H11.5低表达的肾癌患者差。细胞实验和动物实验均证实，下调lncRNA RP11-436H11.5能够抑制肾癌细胞的增殖和侵袭。荧光素酶报告基因实验证实，lncRNA RP11-436H11.5通过调控miR-335-5p的表达来调节BCL-W的表达。lncRNA RP11-436H11.5能够作为miR-335-5p的“诱饵”抑制BCL-W的表达。因此，lncRNA RP11-436H11.5可作为一种竞争性内源性RNA促进肾癌细胞的增殖和侵袭，下调lncRNA RP11-436H11.5的表达可以作为一种抑制肾癌进展的治疗方案。