LncRNA调控子宫内膜癌PTEN表达的分子机制

项目名称： LncRNA调控子宫内膜癌PTEN表达的分子机制

项目编号： No.81202044

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 廖虹

作者单位： 同济大学

项目金额： 23万元

中文摘要： PTEN突变或异常表达是子宫内膜癌发生的重要分子基础，动物模型提示敲除PTEN促进子宫内膜癌发生。我们前期数据提示PTEN在子宫内膜癌中表达下调，而且部分长链非编码RNA(lncRNA)调控PTEN表达，但其分子机制尚待进一步探讨。根据芯片数据和软件分析，部分lncRNA和PTEN具有某些相同microRNA作用位点，因此，我们提出假设：受病理条件或雌激素影响，异常表达的lncRNA通过与PTEN竞争性地结合可作用于两者的microRNA，进而调控PTEN的表达，以及下游PI3K/AKT信号通路和肿瘤的恶性生物学行为。为证实以上假设，我们拟从分子、细胞、组织和整体动物等不同水平，通过正负向调控lncRNA和microRNA，结合RNA-IP、三维立体培养等技术，探讨lncRNA对PTEN的调控机制；同时希望为子宫内膜癌的治疗提供有效的靶标。

中文关键词： 子宫内膜癌；PTEN；长链非编码RNA；假基因；

英文摘要： The mutation of PTEN or aberrant expression play an important role in endometrial cancer development, moreover, the experiment from animal model confirmed that knock out PTEN promote endometrial cancer occur. In our previous and recent work, we found that PTEN was down-regulated in endometrial cancer，more important, parts of lncRNA regulate PTEN expression, but the mechanism is not clear. Base on the result of lncRNA chip assay and prediction of software, some of lncRNA and PTEN have the same microRNA binding element.Therefore, we hypothesis that under pathological and aberrant estrogen condition, aberrant lncRNA regulates PTEN expression by competing binding with microRNA which targeting both lncRNA and PTEN, and subsequently regulates PI3K/AKT signal pathway. To confirm this theory, we will using RIP, real time PCR et. al to investigate the mechanism of lncRNA regulating PTEN from molecular level to tissue level, and to animal model. In addition, we wish we could provide a new insight about the reason of endometrial cancer development and found some of target lncRNA for endometrial cancer therapy.

英文关键词： endometrial cancer；PTEN；lncRNA；pseudogene；