MicroRNA‑144‑3p may participate in the pathogenesis of preeclampsia by targeting Cox‑2

Abstract

Preeclampsia remains a major cause of maternal mortality and morbidity worldwide. It is generally accepted that the development of the placenta, including spiral artery remodelling, normal trophoblast cells function and maternal-fetal inflammation-immune interactions, is critical for the pathogenesis of preeclampsia. Several investigations have demonstrated that microRNAs (miRNAs/miRs) in the placenta may be potential molecular markers for diagnosis of preeclampsia. In the current study, the aim was to investigate the expression of miR-144-3p in the placenta of patients with preeclampsia and normal placentas, and to explore the potential target genes. miRNA microarray analysis was performed using three paired placentas (preeclampsia and normal) in order to find differential expression of miRNAs. Following this, miR-144-3p was selected as a differentially expressed miRNA and validated using in situ hybridization to determine the clinical significance in placentas with preeclampsia. A potential target gene of miR-144-3p, cyclooxygenase-2 (Cox-2), was identified by bioinformatics, luciferase reporter assay and western blotting. The expression of Cox-2 was also examined by immunohistochemical staining of samples of placenta from patients with preeclampsia and normal placenta. Western blot analysis was performed to investigate the effect of miR-144-3p on the expression of Cox-2 in HTR-8/SVneo cells in vitro . miR-144-3p was decreased in placentas from patients with preeclampsia. A luciferase reporter assay demonstrated that Cox-2 was a potential miR-144-3p target gene and the result was verified by western blotting. A negative correlation was observed between miR-144-3p and Cox-2 in preeclamptic placenta by immunohistochemical staining and in situ hybridization. Western blot analysis demonstrated that overexpression of miR-144-3p decreased Cox-2 expression by 38.2% in HTR-8/SVneo cells. Understanding the differential expression of miR-144-3p and its association with Cox-2 may aid the exploration of the pathogenesis of preeclampsia, and contribute to the development of miRNA-based therapies in the future.

RETRACTED ARTICLE: Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosomal MicroRNA-18b-3p Inhibits the Occurrence of Preeclampsia by Targeting LEP

“…Preeclampsia (PE), featured by proteinuria and hypertension [ 1 ], is a major cause of fetal and maternal mortality and morbidity in human pregnancy [ 2 ]. The etiology and pathogenesis of PE are not clear [ 3 ], which has been reported to be associated with abnormal trophoblast invasion resulting in maternal endothelial dysfunction, chronic placental malperfusion and hypertension with adverse outcomes [ 4 ]. With the exception of fetal and placental delivery, there is no specific therapy for PE [ 5 ].…”

miR‐144‐3p ameliorates the progression of osteoarthritis by targeting IL‐1β: Potential therapeutic implications

“…MiR‐144‐3p can also regulate the development and progression of ovarian cancer through suppressing Pre‐B cell leukemia homeobox 3 (PBX3) expression (Li et al, 2020). Moreover, miR‐144‐3p may be involved in the pathogenesis of pre‐eclampsia, as research has found that miR‐144‐3p expression is downregulated in placentas from women with pre‐eclampsia compared with paired normal placentas, and also that miR‐144‐3p is negatively correlated with cyloxygenase‐2 expression, which is known to be increased in the placenta of patients with pre‐eclampsia (Hu et al, 2019). In this study, our bioinformatics analysis revealed that miR‐144‐3p is capable of binding to IL‐1β, and we observed a negative correlation between levels of IL‐1β and miR‐144‐3p in human OA synovial tissue.…”

Insight into the Key Points of Preeclampsia Pathophysiology: Uterine Artery Remodeling and the Role of MicroRNAs

“…Hu et al reported that the expression of miRNA-144-3p was decreased in preeclamptic placentas and it was negatively correlated with placental expression of cyclooxygenase-2 (Cox-2), an enzyme of prostaglandin synthesis, that may play an important role in the development of PE. The association between miRNA-144-3p and Cox-2 was also confirmed in vitro [ 75 ]. Guo et al demonstrated that miRNA-133a-3p can relieve the oxidative stress-induced apoptosis in the trophoblast cells through the BACH1/Nrf2/HO-1 signaling pathway [ 76 ].…”