Down-regulated miR-149-5p contributes to preeclampsia via modulating endoglin expression

Abstract

Objective: Endoglin is expressed in human placenta and plays an important role in the pathogenesis of preeclampsia. Dysregulation of microRNAs in placental tissues has been recently suggested to be involved in the pathogenesis of preeclampsia. Until now, few studies have shed light on the correlation between endoglin and microRNAs, the latter of which may regulate the expression of ENG, a gene encoding endoglin, in placenta. In this study, we aim to investigate the regulation of ENG by microRNAs.

Study design: We located the microRNAs that might regulate the expression of ENG. Candidate microRNAs were tested if they had an impact on trophoblast function.

Main outcome measures: We compared endoglin expression between normotensive and preeclamptic placentas by using immunohistochemistry and real-time PCR. Downregulated microRNAs in preeclamptic placenta were revealed from a literature review. A bioinformatics assay was performed to predict those that might target ENG. Real-time PCR, Western blotting and dual luciferase assay were used to verify the targeting. The effects of the microRNAs on trophoblasts were evaluated by transwell invasion assay.

Results: The endoglin level was significantly higher in preeclamptic placenta than in normotensive placenta. ENG was validated as the direct target of miR-149-5p and was inversely correlated with it. MiR-149-5p promoted the invasion of trophoblast cells, and this promotion was abrogated by the overexpression of ENG.

Conclusions: Our findings highlight the importance of miR-149-5p in the pathogenesis of preeclampsia and provide new insight into the development of the disease.

Keywords: Endoglin; Invasion; Preeclampsia; Trophoblast; miR-149-5p.