MiR-942 decreased before 20 weeks gestation in women with preeclampsia and was associated with the pathophysiology of preeclampsia in vitro

Abstract

Objective: To investigate the possible relationship between miR-942 levels and the pathogenesis of preeclampsia using in vitro assays and to investigate circulating miR-942 levels in the early phase of mid-of pregnancy in women who later developed preeclampsia and in women with uncomplicated pregnancies. Methods: Plasma samples were collected from pregnant women between 12 and 20 weeks of gestation. MiR-942 levels were determined by stem-loop real-time PCR for 26 cases who subsequently developed preeclampsia as well as for 52 controls. Bioinformatics software was used to predict the target genes of miR-942, and a dual-luciferase reporter system was utilized to validate target gene regulation. Finally, MTT proliferation assays, transwell invasion assays, and endothelial cell tube formation assays were performed to further explore the function of miR-942 using a human extravillous trophoblast cell line (TEV-1). Result: Circulating miR-942 levels were significantly lower in mid-pregnancy (12–20 weeks gestation) in women who later developed preeclampsia compared with those with an uncomplicated pregnancy (p < 0.05). Endoglin (ENG) is an miR-942 target gene. MiR-942 had a sensitivity of 0.673, a specificity of 0.875, and an area under the receiver operating characteristic curve (AUC) of 0.718 [95% CI, 0.594–0.822] for the possible screening of preeclampsia. In vitro, decreased miR-942 expression decreased the invasive ability of TEV-1 cells, and inhibited the HUVEC angiogenesis assay, both effects that are similar to what is observed in preeclampsia (both p <0.05). Conclusion: MiR-942 may be involved in the pathogenesis of preeclampsia via the regulation of its target gene ENG. Multicenter studies must be performed and a greater number of samples must be analyzed to ascertain whether circulating miR-942 levels can serve as a novel early diagnostic marker for preeclampsia.

Keywords

• endoglin
• early diagnosis
• mir-942
• preeclampsia
• plasma marker