MicroRNAs (miRNAs) are emerging as novel modulators in the pathogenesis of preeclampsia (PE). Multiple miRNAs have been shown to regulate the proliferation and invasion of trophoblast cells, which play a critical role in successful pregnancies. miR-652-3p has been identified as a novel disease-associated miRNA that is dysregulated in various pathological processes. However, whether miR-652-3p is dysregulated in PE and regulates the cellular function of trophoblast cells remains unknown. In the present study, we aimed to investigate the expression pattern of miR-652-3p in PE and explore its potential function in trophoblast cells. Herein, we found that miR-652-3p expression was significantly decreased in the placental tissues of pregnant women with PE. Cellular function experiments showed that overexpression of miR-652-3p promoted the viability, proliferation, and invasion of trophoblast cells in vitro. By contrast, inhibition of miR-652-3p had the opposite effect. Bioinformatics analysis predicted that homeobox A9 (HOXA9), a crucial regulator of trophoblast cell function, was a potential target gene of miR-652-3p. A luciferase reporter assay confirmed that miR-652-3p directly interacted with the 3'-untranslated region of HOXA9. Moreover, miR-652-3p was shown to negatively regulate the expression of HOXA9 and ephrin receptor B4 (EphB4) in trophoblast cells. Notably, overexpression of HOXA9 or EphB4 significantly reversed the regulatory effect of miR-652-3p on proliferation and invasion of trophoblast cells. Taken together, our findings demonstrate that miR-652-3p regulates the proliferation and invasion of trophoblast cells, possibly through targeting HOXA9 and modulating EphB4 expression.
Keywords: EphB4; HOXA9; miR-652-3p; preeclampsia; trophoblast.
© 2019 John Wiley & Sons Australia, Ltd.