MicroRNA-491-5p inhibits trophoblast cell migration and invasion through targeting matrix metalloproteinase-9 in preeclampsia

Insufficient invasion of trophoblasts is correlated with the development of preeclampsia (PE). MicroRNA (miR)-491-5p has been reported to be implicated in human cancer cell invasion; however, whether miR-491-5p is involved in the development of PE remains largely unclear. The aim of the present study was to investigate the role of miR-491-5p in trophoblastic invasion in vitro and to determine its underlying mechanism of action. The expression levels of miR-491-5p were validated using reverse transcription-quantitative PCR. The effects of miR-491-5p on trophoblast cell invasion were evaluated in vitro. Then, the association between miR-491-5p and its downstream target was investigated in both cell lines and clinical specimens. miR-491-5p expression levels were observed to be significantly increased in the placental tissues from patients with PE. The invasive capacity of HTR-8/SVneo trophoblast cells was suppressed following the upregulation of miR-491-5p and increased following the inhibition of miR-491-5p. Matrix metalloproteinase-9 (MMP-9), a well-known regulator of trophoblast cell invasion, was discovered to be a direct target of miR-491-5p in HTR-8/SVneo trophoblast cells. Moreover, miR-491-5p expression levels were found to be inversely correlated with MMP-9 expression levels in placental tissues from patients with PE. The overexpression of MMP-9 partly attenuated the inhibitory effects of miR-491-5p on HTR-8/SVneo trophoblast cells invasion. Collectively, these findings suggested that the aberrant expression of miR-491-5p may contribute to PE through suppressing trophoblast invasion, thus highlighting the novel roles of miR-491-5p in the molecular pathogenesis of PE. The present study also showed that the miR-491-5p/MMP-9 axis may be an effective biomarker or a viable drug target for therapeutic intervention in PE.