Mounting evidence has revealed that impaired spiral artery remodeling, placental dysfunction, and inadequate trophoblast invasion are closely correlated with the etiology and pathogenesis of pre-eclampsia (PE). Moreover, defective trophoblast invasion may trigger poor maternal–fetal circulation and placental hypoxia, leading to PE. However, the detailed molecular pathology of PE remains unclear. Although circRNAs, as a new type of stable and abundant endogenous noncoding RNA, have been proven to be essential to the pathogenesis of various diseases, their role in PE requires further verification. In this context, it is necessary to unveil the roles of circRNAs in regulating the migration and invasion of extravillous trophoblasts. In this study, using quantitative real-time PCR, we confirmed that hsa_circ_0111277 was upregulated in PE placentas relative to the level in normal pregnancy placentas. In addition, positive correlations between hsa_circ_0111277 expression and PE-related factors (proteinuria level at 24 h and placental weight) were identified by Pearson’s analysis based on the clinical data of 25 PE patients. Moreover, fluorescence in situ hybridization analysis illustrated that circ_0111277 was preferentially localized within the cytoplasm. Mechanistically, circ_0111277 sponged hsa-miR-494-3p in trophoblast cells to attenuate the latter’s repression by regulating HTRA1/Notch-1 expression. In conclusion, trophoblast cell migration and invasion were shown to be promoted and modulated by the hsa_circ_0111277/miR-494-3p/HTRA1/Notch-1 axis, which provides useful insight for exploring a new therapeutic approach for PE.

越来越多的证据表明，螺旋动脉重塑受损、胎盘功能障碍和滋养层侵袭不足与先兆子痫（PE）的病因和发病机制密切相关。此外，滋养层侵袭缺陷可能引发母胎循环不良和胎盘缺氧，导致PE。然而，PE 的详细分子病理学仍不清楚。尽管circRNA作为一种稳定且丰富的新型内源性非编码RNA，已被证明对多种疾病的发病机制至关重要，但其在PE中的作用还需要进一步验证。在这种背景下，有必要揭示circRNA在调节绒毛外滋养细胞迁移和侵袭中的作用。在本研究中，使用定量实时 PCR，我们证实 hsa_circ_0111277 在 PE 胎盘中相对于正常妊娠胎盘中的水平上调。此外，Pearson根据25例PE患者的临床数据进行分析，发现hsa_circ_0111277表达与PE相关因素（24小时蛋白尿水平和胎盘重量）呈正相关。此外，荧光原位杂交分析表明，circ_0111277优先定位于细胞质内。从机制上讲，circ_0111277 在滋养层细胞中吸收 hsa-miR-494-3p，通过调节 HTRA1/Notch-1 表达来减弱后者的抑制。总之，滋养层细胞迁移和侵袭被hsa_circ_0111277/miR-494-3p/HTRA1/Notch-1轴促进和调节，这为探索PE的新治疗方法提供了有用的见解。