hsa_circ_0007121是我们前期通过高通量RNA测序筛选出的新环状RNA，已证实其在子痫前期（PE）胎盘组织中表达下调，且此种下调在PE孕妇妊娠14-18周的外周血中即可检出，提示其参与PE早期发病。由于其功能未知，本项目通过系列研究，提出hsa_circ_0007121这一新的氧化应激感受器参与PE发病的可能途径：通过海绵吸附miR-323-3p靶向调控β-catenin基因；或与功能蛋白Dickkopf-1互作，最终导致滋养细胞生物学功能损伤。本项目拟沿用已构建的PE体外研究模型（原代EVT和绒毛外植体）和eNOS基因敲除孕鼠模型，从细胞-组织-动物三个层次揭示以hsa_circ_0007121为核心的PE早期病因学网络；同时依托前瞻性PE妊娠队列，结合数学建模评估hsa_circ_0007121作为PE早期预测及预后判定标志物的效能，以期为PE早期预测和防治提供新的靶点。

Hsa_circ_0007121,a novel circular RNA(circRNA) screened by high throughput RNA sequencing in our previous study, has been validated downregulated in placenta of preeclampsia(PE) and this dysregulation could be tested from maternal peripheral blood samples obtained at 14-18 weeks of gestation. These results revealed that hsa_circ_0007121 might participate in pathogenesis of PE in the early stage. Although functions of this circRNA have not been reported so far, based on our previous research, we hypothesized that hsa_circ_0007121 could induce pathogenesis of PE as a new oxidative stress sensor through two pathways: sponging miR-323-3p and/or interacting with Dickkopf-1 protein to regulate β-catenin and causing dysfunctions of trophoblasts finally. We will systematically investigate pathogenesis networks of hsa_circ_0007121 participating in PE through series experiments based on cell, tissue and animal levels using in vitro(primary extravillous trophoblast and villous explants) and in the vivo models(eNOS knock-out pregnancy mice) established previously. Besides, a prospective cohort study of PE and mathematical model will be performed to evaluate the predictive and prognosis estimation efficiency of hsa_circ_0007121, and identify new intervention targets for early prediction and prevention of preeclampsia, expectantly.