Abstract
Our study was approved by the Medical Ethics Committee of Tang Du Hospital, Fourth Military Medical University and complied strictly with national ethical guidelines. Preeclampsia (PE) is a specific clinical disorder characterized by gestational hypertension and proteinuria and is a leading cause of maternal and perinatal mortality worldwide. The miR-519d-3p is upregulated in the maternal plasma of patients with PE which indicates a possible association between this microRNA and the pathogenesis of PE. No studies to date have addressed the effect of miR-519d-3p on the invasion and migration of trophoblast cells. In our study, we found that miR-519d-3p expression was elevated in placental samples from patients with PE. In vitro, overexpression of miR-519d-3p significantly inhibited trophoblast cell migration and invasion, whereas transfection of a miR-519d-3p inhibitor enhanced trophoblast cell migration and invasion. Luciferase assays confirmed that matrix metalloproteinase-2 (MMP-2) is a direct target of miR-519d-3p. Quantitative real-time PCR and western blot assays showed that overexpression of miR-519d-3p downregulated MMP-2 mRNA and protein expression. Knockdown of MMP-2 using a siRNA attenuated the increased trophoblast migration and invasion promoted by the miR-519d-3p inhibitor. In placentas from patients with PE or normal pregnancies, a negative correlation between the expression of MMP-2 and miR-519d-3p was observed using the Pearson correlation and linear regression analysis. Our present findings suggest that upregulation of miR-519d-3p may contribute to the development of PE by inhibiting trophoblast cell migration and invasion via targeting MMP-2; miR-519d-3p may represent a potential predictive and therapeutic target for PE.
Highlights
Preeclampsia (PE) is a specific disorder characterized by gestational hypertension and proteinuria as the main clinical symptoms [1]
We found that miR-519d-3p was overexpressed in the placentas of patients with PE, and downregulated in a trophoblast tumor cell line compared to a normal trophoblast cell line
We proved that miR-519d-3p could suppress the invasion and migration of trophoblast cells via targeting matrix metalloproteinase-2 (MMP-2) using in vitro functional and rescue experiments
Summary
Preeclampsia (PE) is a specific disorder characterized by gestational hypertension and proteinuria as the main clinical symptoms [1]. The exact pathophysiological mechanism leading to PE remains uncertain, it is generally considered that PE is a multifactorial disorder with placental oxygen disruption [2], inappropriate maternal vascular damage [3], anomalous maternal-fetal immune interactions [4,5], abnormal trophoblast cell invasion [6], and other processes involved. Recent reports have shown that matrix metalloproteinase-2 (MMP-2), an important zinc-dependent protease in the MMP superfamily that breaks down extracellular matrix components [7], may be involved in cytotrophoblastic invasion during embryogenesis. Dysregulation of MMP-2 expression and impaired MMP-2 activity are involved in abnormal uteroplacental artery remodeling and trophoblastic invasion in hypertension of pregnancy [8]. The potential effects and mechanisms by which miRNAs regulate trophoblastic cell function are poorly characterized and need to be investigated further
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
