长链非编码RNA DANCR作为ceRNA调控ROCK1介导骨肉瘤侵袭转移作用机制研究

项目名称： 长链非编码RNA DANCR作为ceRNA调控ROCK1介导骨肉瘤侵袭转移作用机制研究

项目编号： No.81502333

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 王勇

作者单位： 沈阳医学院

项目金额： 18万元

中文摘要： ROCK1介导骨肉瘤侵袭转移。长链非编码RNA DANCR参与成骨细胞和前体细胞分化的调控，但在ROCK1介导骨肉瘤的侵袭转移中的作用与机制不清。申请者发现DANCR在骨肉瘤组织和细胞中高表达，沉默DANCR后，骨肉瘤细胞侵袭转移能力下降，同时ROCK1表达降低；骨肉瘤细胞中ROCK1是miR-335靶基因之一；理论预测DANCR存在与miR-335结合位点，提示DANCR可能作为ceRNA调控ROCK1表达，影响骨肉瘤的侵袭转移。本项目拟确认DANCR与miR-335特异结合作用及关键位点，考察 DANCR调控骨肉瘤细胞侵袭转移与ROCK1表达的相关性，研究DANCR作为ceRNA 竞争性调控 ROCK1介导的骨肉瘤侵袭和转移，并在裸鼠转移瘤模型上进行验证，为寻找骨肉瘤侵袭转移形成与逆转的新靶点、进一步阐明骨肉瘤发生发展机制奠定理论与实验基础。

中文关键词： 长链非编码RNA；DANCR；骨肉瘤；竞争性內源RNA；ROCK1；侵袭转移

英文摘要： ROCK1 mediates migration and invasion in osteosarcoma. Long non-coding RNA DANCR participates in regulation of osteoblast and precursor cell differentiation but the function and mechanism it plays in osteosarcoma migration and invasion mediated by ROCK1 remains unclear. The proposer found higher DANCR expression in osteosarcoma tissues and cells. The migration and invasion ability was down-regulated while ROCK1 expression was decreased when silence of DANCR in osteosarcoma cells. ROCK1 is one of target genes of miR-335. We theoretically predicted DANCR could bind to miR-335 and this may indicate us DANCR may regulate ROCK1 expression as ceRNA and effect migration and invasion in osteosarcoma. Our project intends to affirm the specific binding effect and the key binding-region between miR-335 and DANCR，investigate the correlation DANCR regulating migration/invasion and the expression of ROCK1 in osteosarcoma and to study the mechanism of DANCR regulating migration/invasion mediated by ROCK1 as ceRNA, while, to testify the effect in naked mice models. Our project aims at laying the further theoretical and experimental foundation of clarifying the developmental mechanism and finding out new target spot to reverse the formation of osteosarcoma.

英文关键词： long non-coding RNA DANCR;osteosarcoma;competing endogenous RNA;ROCK1;migration and invasion