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. H I Ì R N A 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 H I Ì R N A 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 demon¬ strated 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.