LncRNA-TC0101441抑制KiSS-1促进卵巢癌侵袭转移的作用及分子机制

项目名称： LncRNA-TC0101441抑制KiSS-1促进卵巢癌侵袭转移的作用及分子机制

项目编号： No.81502240

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： 邱君君

作者单位： 复旦大学

项目金额： 18万元

中文摘要： 卵巢癌转移是影响预后的关键。申请人前期发现的新长链非编码RNA（lncRNA-TC0101441）能介导雌激素的促卵巢癌转移效应。新近实验进一步发现TC0101441与卵巢癌不良预后有关，促进卵巢癌的侵袭转移；且与临近靶基因KiSS-1表达呈负相关。在此基础上，本项目拟：在临床、细胞、动物水平，阐明TC0101441通过抑制KiSS-1促进卵巢癌侵袭转移的作用；分析TC0101441、KiSS-1成为预测卵巢癌预后、复发指标的可能性；通过截取不同长度启动子序列、构建野生及突变型载体、荧光素酶报告基因实验、RNA pulldown与质谱分析、RIP、EMSA及ChIP等技术，阐明TC0101441干扰Sp1对KiSS-1的转录调控，抑制KiSS-1表达的分子机制。这些原创性研究将从lncRNA角度为卵巢癌转移阐释新的调控机制，为卵巢癌的预后判断及个体化治疗提供基于lncRNA的新靶点。

中文关键词： 卵巢肿瘤；长链非编码RNA；KiSS-1；Sp1；转移

英文摘要： The survival rate of ovarian cacer is poor. Such an unfavourable prognosis has been largely correlated with the tumour metastasis. The applicant had ever identified a new lncRNA (lncRNA-TC0101441) and found that TC0101441 contributed to E2-induced ovarian cancer cell invasion/migration. Recently, our preliminary experiments showed that TC0101441 correlated with poor prognosis of ovarian cancer, promoted cell invasion/migration and inhibited the expression of its target gene KiSS-1 in ovarian cancer cells. Based on these observations, in this project, we will use human clinical samples, in vitro studies and in vivo animal models to elucidate that TC0101441 can promote ovarian cancer cell invasion/migration partially through the suppression of its target gene KiSS-1 and that both TC0101441 and KiSS-1 may serve as independent predictors for overall survival. Moreover, we will demonstrate that TC0101441 can interact with Sp1 to form transcription complexes at specific Sp1-binding sites of the promoter to inhibit KiSS-1 transcription and explore the underlying molecular mechanism. These original researches may shed a new insight into the mechanism of ovarian cancer metastasis by providing a perspective of lncRNA and provide a rationale for the development of lncRNA-based targeted approaches for the treatment and prognosis estimation of ovarian cancer.

英文关键词： ovarian cancer;long noncoding RNA;KiSS-1;Sp1;metastasis