Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
Institute of Molecular and Medical Virology, School of Medicine, Jinan University, Guangzhou, 510632, China.
Placenta. 2024 Oct;156:67-76. doi: 10.1016/j.placenta.2024.09.007. Epub 2024 Sep 10.
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.
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.
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.
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.
胎盘滋养层功能障碍与子痫前期的发病机制密切相关。冠状蛋白样肌动蛋白结合蛋白 1C（CORO1C）在细胞增殖、凋亡、侵袭和信号转导中发挥重要作用，但它在滋养层功能障碍和子痫前期中的作用尚不确定。
采用实时定量聚合酶链反应（RT-qPCR）、Western blot（WB）和免疫组织化学（IHC）染色检测子痫前期（PE）孕妇和 PE 小鼠模型胎盘组织中 CORO1C 的表达。接下来，进行了 CORO1C 在 HTR8/SVneo 细胞中的增殖、侵袭、迁移和凋亡实验，以探讨 CORO1C 的功能。此外，在 lncMALAT1 敲低和过表达 HTR-8/SVneo 细胞中检测 CORO1C 的表达。然后，我们通过生物信息学分析、FISH 实验、RIP 实验、RNA 下拉和双荧光素酶报告基因实验研究了 lncMALAT1 对 CORO1C 的可能调控机制。最后，我们进一步验证了 lncMALAT1 通过 CORO1C 调节胎盘滋养层细胞的功能。
PE 患者和小鼠模型胎盘组织中 CORO1C 的表达明显降低，且与新生儿出生体重呈正相关。我们发现 CORO1C 抑制滋养层细胞的增殖、迁移和侵袭。此外，lncMALAT1 表达下调降低了 CORO1C 水平，从而导致滋养层细胞功能障碍。机制上，lncMALAT1 的失调促进了 miR-133a-3p 的表达，从而增强了其与 CORO1C mRNA 3'UTR 区域的结合进行降解。
本研究表明，lncMALAT1 通过 CORO1C/miR-133a-3p 轴的失调会损害滋养层功能，导致子痫前期的发病机制，通过调节 CORO1C 水平为 PE 治疗提供了新的思路。
