MicroRNA-652-3p promotes the proliferation and invasion of the trophoblast HTR-8/SVneo cell line by targeting homeobox A9 to modulate the expression of ephrin receptor B4.

Abstract

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.