Cir-TBC1D1靶向EPHB4在孕早期不明原因复发性流产中作用机制研究

不明原因复发性流产（URSA）是一种病理性妊娠，其病因和发病机制一直是生殖领域研究的热点。近年研究发现，环状RNA(circRNA)作为一类非编码RNA新家族，在胚胎生长发育过程中起重要的调控作用。我们前期研究发现circ-TBC1D1、miR-520h、EPHB4与URSA存在相关性，通过生物信息学预测及临床初步验证circ-TBC1D1可能靶向miR-520h/EPHB4参与胚胎发育调控。本课题拟从临床研究、细胞水平及URSA小鼠模型论证circ-TBC1D1对胚胎发育的影响，阐明 circ-TBC1D1可能作为ceRNA竞争性结合miR-520h 从而调控EPHB4基因，影响绒毛血管生成，参与URSA病理生理过程，本课题首次用ceRNA海绵机制力图阐释URSA以及血管生成机制，为防治USRA提供理论基础及新的药物靶点。

Unexplained recurrent abortion (URSA) is a kind of pathological pregnancy.Its etiology and pathogenesis have always been the focus of reproductive research. In recent years, circRNA, as a new non-coding RNA family, plays an important role in the regulation of embryo growth and development. Our previous study found that circ-tbc1d1, mir-520h and EPHB4 were correlated with URSA. Through bioinformatics prediction and preliminary clinical verification, circ-tbc1d1 may be involved in the regulation of embryonic development by targeting mir-520h /EPHB4. We plan to investigate the effect of circ-tbc1d1 on embryonic development from clinical studies, cytological experiments and the construction of URSA mouse model, and clarified that circ-tbc1d1 may act as a competitive binding of ceRNA to mir-520h to regulate EPHB4 gene, affect villi angiogenesis, and participate in the pathophysiological process of URSA, In this study, the ceRNA sponge mechanism was used for the first time to try to explain URSA and the angiogenesis mechanism, so as to provide a theoretical basis and a new drug target for the prevention and treatment of USRA.