Circ0111277编码新蛋白PAPPA2-171aa阻断Hippo-YAP1通路抑制子痫前期滋养层浸润的机制研究

环状RNA能否编码功能蛋白及其在子痫前期（PE）中的作用不明。前期研究，我们首次发现了一个由circ0111277基因编码的全新功能蛋白PAPPA2-171aa；PAPPA2-171aa由跨环状接口的开放读码框翻译，对滋养细胞侵袭有明显抑制作用；转录组测序及过表达验证发现PAPPA2-171aa可能介导Hippo通路效应蛋白YAP1磷酸化失活。据此提出科学问题：circ0111277是否依赖于编码PAPPA2-171aa阻断Hippo-YAP1通路抑制胎盘滋养层浸润诱发PE？本研究拟通过Co-IP及质谱、荧光素酶报告基因、ChIP、RNA pull-down，从滋养细胞、绒毛膜外植体、动物模型层面阐明circ0111277编码PAPPA2-171aa抑制PE滋养层浸润的机制，探索PAPPA2-171aa的临床意义与转化应用前景，为将环状RNA编码的蛋白应用于PE早期预测及诊疗打下理论基础。

Up-to-data, whether circular RNA could encode functional proteins or its roles in preeclampsia remains unknown. In previous study, we identified a circular RNA （circ0111277） gene encoded novel functional protein PAPPA2-171aa for the first time. Containing the circular specific amino acid, PAPPA2-171aa strongly suppressed trophoblast infiltration in vitro. Through RNA-seq and over-expression verification, we found that PAPPA2-171aa may mediate the phosphorylation inactivation of Hippo pathway effector protein YAP1. Therefore, we proposed the scientific question: Does circ0111277 reply on PAPPA2-171aa to block the Hippo-YAP1 pathway and suppress trophoblast infiltration in preeclampsia? Through CO-IP and LC-MS/MS, Luciferase reporter gene, ChIP and RNA pull-down, this study is designed to clarify the mechanism of PAPPA2-171aa encoded by circ0111277 suppressing trophoblast infiltration from trophoblast cells, chorionic explants and animal models, and explore the clinical and translational implications of PAPPA2-171aa in preeclampsia. Through current study, we hope to lay the foundation of using circular RNA translated proteins for the future early prediction、diagnosis and treatment of preeclampsia.