Circular RNA circ_0111277 attenuates human trophoblast cell invasion and migration by regulating miR-494/HTRA1/Notch-1 signal pathway in pre-eclampsia

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.