Down-regulation of CORO1C mediated by lncMALAT1/miR-133a-3p axis contributes to trophoblast dysfunction and preeclampsia.

Introduction: Placental trophoblast dysfunction has been proved to be closely related to the pathogenesis of preeclampsia. Coronaryxin-like actin-binding protein 1C (CORO1C) plays an important role in cell proliferation, apoptosis, invasion, and signal transduction, but its involvement in trophoblast dysfunction and preeclampsia remains uncertain.

Methods: The expression of CORO1C in placental tissues of preeclampsia (PE) pregnant women and pregnant mice PE model were detected by real-time quantitative polymerase chain reaction (RT-qPCR), western blotting (WB) and immunohistochemical (IHC) staining. Next, the proliferation, invasion, migration and apoptosis were performed to explore the functions of CORO1C in HTR8/SVneo cell. Furthermore, the expression of CORO1C were detected in lncMALAT1 knockdown and overexpression HTR-8/SVneo cell. And then we investigated the possible regulatory mechanism of lncMALAT1 on CORO1C through bioinformatics analysis, FISH assays, RIP assays, RNA pull down and dual luciferase reporter assays. Finally, we further validated that lncMALAT1 regulate the function of placental trophoblast cells through CORO1C.

Results: The expression of CORO1C was significantly decreased in the placenta of PE patients and mice model, and positively associated with neonatal birth weight. And we found that CORO1C inhibited trophoblast proliferation, migration and invasion. Furthermore, reduced expression of lncMALAT1 impaired CORO1C level, thereby resulting in trophoblast dysfunction. Mechanistically, the dysregulation of lncMALAT1 promoted the expression of miR-133a-3p, strongly enhancing its binding to the 3'UTR region of CORO1C mRNA for degradation.

Discussion: This study demonstrated that the dysregulation of CORO1C via lncMALAT1/miR-133a-3p axis impairs trophoblast function and contributes to preeclampsia pathogenesis, providing novel insights in PE therapy through modulating CORO1C level.