microRNA‑21 regulates the proliferation of placental cells via FOXM1 in preeclampsia

Abstract

The present study determined the expression of microRNA (miRNA or miR)-21 and forkhead box M1 (FOXM1) in placenta and blood samples from patients with preeclampsia (PE), and investigated the relationship between miR-21 and FOXM1. A total of 32 pregnant women with PE and 28 healthy pregnant women were included in the study as the experimental and control groups, respectively. Placental tissues and peripheral blood were collected from all subjects. ELISA was performed to measure the level of FOXM1 protein in the blood. HTR8/SVneo cells overexpressing miR-21 were established by transfection with agomiR-21. Reverse transcription-quantitative PCR was performed to measure the expression of FOXM1 mRNA and miR-21 in the placenta, blood and cells, and western blotting was used to evaluate FOXM1 protein expression in the placenta. An MTT assay was also performed to assess cell viability. In addition, a dual-luciferase reporter assay was used to investigate the direct interaction between FOXM1 and miR-21. The occurrence of PE was found to be associated with reduced FOXM1 mRNA levels, and elevated FOXM1 protein expression may serve a regulatory role that when attenuated leads to the occurrence of PE. Furthermore, miR-21 may serve a regulatory role in the pathology of PE by downregulating FOXM1 expression at the transcriptional level. In HTR8/SVneo cells, the overexpression of miR-21 reduced cell viability, possibly via the reduction of FOXM1 expression. The dual-luciferase assay indicated that miR-21 directly binds to the 3'-untranslated region of FOXM1 to regulate its expression. The present study demonstrated that the expression of FOXM1 mRNA and protein is downregulated, whereas the expression of miR-21 is upregulated in the placenta and blood samples of PE patients. In conclusion, miR-21 may regulate placental cell proliferation via its effects on FOXM1 to promote the occurrence and development of PE.

MiRNA Profiling in Plasma and Placenta of SARS-CoV-2-Infected Pregnant Women

“…Even more importantly, we cannot forget that the expression of almost all of these miRNAs has also been conveyed in pregnancy-associated disorders. For example, miR-21, miR-29, miR-150 and miR-155 are highly expressed in human placentae of preeclampsia patients [ 44 , 45 , 46 ]; aberrant expression of miR-21 was reported to be associated with foetal hypoxia, foetal growth restriction, and macrosomia [ 47 , 48 , 49 ]; mir-29, miR-98 were upregulated in placentas from gestational diabetes mellitus patients [ 50 , 51 ]. For all these reasons, although the induction of these miRNAs has been associated with an effective control of viral replication, and no SIPW enrolled in this study had obstetric pathology related to placental malfunction, we cannot exclude that the alteration of miRNA profile might result from pregnancy-related complications.…”

Association of Circulating miRNA Expression with Preeclampsia, Its Onset, and Severity

“…Studies focused on the association between miR-21 expression and PE presented inconsistent results. Some studies reported overexpression of miR-21 in PE placentas [ 47 , 48 ], and also in maternal plasma or serum of PE patients [ 43 , 48 ]. Results of the study by Jairajpuri et al (2017) depicted upregulation of circulating miR-21 in the plasma of patients with severe PE compared to the mild form [ 43 ].…”

Defective Uteroplacental Vascular Remodeling in Preeclampsia: Key Molecular Factors Leading to Long Term Cardiovascular Disease

“…The role of miR-21 in preeclampsia has been also newly studied, since it regulates the forkhead box M1 protein (FOXM1), which is expressed in cytotrophoblasts for proliferation and differentiation, responsible for the early placental development [ 93 ]. In fact, a study showed that miR-21 is elevated with reduced FOXM1 expression in patients with preeclampsia compared to those in normotensive pregnant women, implying that miR-21 may impede the early placental invasion leading to preeclampsia [ 94 ]. These results demonstrate that various miRNAs are involved in the pathway of preeclampsia which implies their potential to become possible future therapeutic targets for treatment of preeclampsia.…”