Abstract

Preeclampsia (PE), a pregnancy-related multisystem syndrome, is one of the leading causes of maternal and fetal mortality worldwide. The aim of this study was to combine the plasma protein soluble Fms-related tyrosine kinase 1 (sFLT1) levels with uterine artery Doppler ultrasound findings and CircBRAP levels during the first trimester to predict the occurrence of preeclampsia and to explore the potential mechanism by which CircBRAP functions in preeclampsia. Here, we used qRT-PCR to investigate the expression of CircBRAP in forty-nine pairs of plasma specimens and placental tissues from preeclampsia patients and control subjects. The uterine artery (UtA) pulsatility index (PI) was measured using four-dimensional color Doppler ultrasound, and the sFLT1 levels were evaluated by human immunoassay. Exogenous upregulation or downregulation of CircBRAP expression in TEV-1 trophoblast cells was performed to investigate the role of CircBRAP in cell biological behavior. Mechanistically, luciferase reporter, RNA immunoprecipitation (RIP), and biotin-coupled RNA pull-down assays were conducted to verify the relationship between CircBRAP and sFLT1 in TEV-1 cells. The results showed that the predictive power was strengthened when the plasma sFLT1 and CircBRAP levels were combined with the UtA-PI to predict preeclampsia occurrence. Our study also revealed that CircBRAP may regulate miR-106b and the HIF-2α axis to modulate the proliferation, invasion, and apoptosis of TEV-1 trophoblast cells. In summary, placenta-derived CircBRAP in plasma may be a novel biomarker for preeclampsia that, together with plasma sFLT1 levels and uterine artery Doppler ultrasound findings, can more effectively predict preeclampsia, and CircBRAP may play a potential role in preeclampsia.