子痫前期(PE)对孕产妇、胎儿及新生儿危害巨大。已有报道，microRNA调控紊乱在PE发生中扮演关键作用，而多个miRNAs如何协同参与这一过程却知之甚少。我们前期研究显示PE胎盘上调表达的miR-193b-3p-miR-31-5p，协同作用于靶基因RIMS3，形成表达调控网络，且其表达水平影响胎盘滋养层细胞功能。本课题拟回答：miR-193b-3p-miR-31-5p-RIMS3调控网络如何参与胎盘形成过程导致PE发生。研究将以临床胎盘组织和细胞系/原代培养细胞为基础，利用免疫共沉淀、质谱等技术，首先阐明上述调控网络的作用方式与功能机制；其次利用转录组测序等技术，筛选两个miRNAs协同作用的其它靶基因及相关信号通路；最后通过滋养层干细胞裸鼠侵袭及小鼠动物模型，探讨上述网络异常对早期妊娠及PE相关临床表型的影响。此研究结果有望为PE的诊疗提供潜在新靶点和理论依据。

Preeclampsia (PE) is a leading cause of maternal mortality worldwide. microRNAs are considered to be important factors during placentation. The abnormalities of these epigenetic regulation contribute to the progression of PE. We have detected miR-193b-3p-miR-31-5p were up-regulated and RIMS3 was down-regulated in PE placenta. miR-193b-3p decreased the migration and proliferation of trophoblast cells in our previous study. RIMS3 was observed as a co-target of miR-193b-3p-miR-31-5p in trophoblast cells. In current study, we will study the function and mechanism of a regulatory network of miR-193b-3p-miR-31-5p-RIMS3 in trophoblast cells. We will study the role of RIMS3 in trophoblast cells. We will also study other targets which were synergistically targeted by miR-193b-3p-miR-31-5p and their function in PE placeta. Finally we will explore the role of miR-193b-3p-miR-31-5p-RIMS3 in early pregnancy through Trophoblast stem cells (TSC) Transplantation and mouse model. This will be beneficial to PE therapeutics.