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

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.