应用宫内孕激素上调miR-197、影响子宫肌瘤细胞增殖与凋亡功能的机制研究

项目名称： 应用宫内孕激素上调miR-197、影响子宫肌瘤细胞增殖与凋亡功能的机制研究

项目编号： No.81202042

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： 徐青

作者单位： 南京医科大学

项目金额： 23万元

中文摘要： miR-197是应用miRNA芯片筛选的一条在孕激素干预UtLMCs中显著上调的miRNA。预研发现：miR-197过表达促进UtLMCs凋亡；高浓度孕激素促进UtLMCs中 miR-197表达上调；生物信息学预测E2F7是miR-197靶基因， 高表达miR-197后引起E2F7表达下调。我们提出miR-197通过调控E2F7参与孕激素影响子宫肌瘤增殖、凋亡的学术思想。本研究拟观察miR-197过表达、表达沉默时对孕激素干预的UtLMCs增殖、凋亡的影响及E2F7的变化；采用表达载体构建或RNAi技术，判断miR-197对 E2F7的作用；最后采用荧光素酶验证其调控作用。由于miR-197受孕激素调控、影响UtLMCs增殖凋亡功能的研究目前尚未见报道，因此具有源头创新性。研究若成功，可为子宫肌瘤防治提供新靶标。

中文关键词： 子宫肌瘤；孕激素；非编码RNA；增殖；凋亡

英文摘要： Previous research has demonstrated via microarray technique that the micro RNA miR-197 is significantly up-regulated in the uterine leiomyoma cells (UtLMCs) after progestin treatment. The research reveals higher concentration of progestin up-regulates miR-197 expression in UtLMCs and over-expression of miR-197 induces UtLMC's apoptosis. Bio-infomation suggests E2F7 is the target gene for miR-197 and over-expression of miR-197 will down-regulate E2F7. We proposes the progestin-induced miR-197 plays a significant role on leiomyoma cells proliferation and apoptosis via the regulation of E2F7. The research will study these influential mechanisms on UtLMCs in relation with the change of E2F7 under the circumstances of over-expression or down-regulation of miR-197. The influential role on E2F7 by miR-197 will also be examined by the construction of specific vectors and RNA interfering technique. The results are to be verified by using luciferase report system. The concept that miR-197 influences UtLMCs apoptosis or proliferation after progestin treatment has not been reported elsewhere. The innovative proposal by this study could possibly find a new target gene for the treatment of uterine leiomyoma.

英文关键词： uterine leiomyoma；progesterone；non-coding RNA；proliferation；apoptosis