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

Abstract

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.

Abnormal expression of SLIT3 induces intravillous vascularization dysplasia in ectopic pregnancy

“…In cancer cells, miR-491-5p induces apoptosis and suppresses proliferation and invasion ( Denoyelle et al., 2014 ; Zhou et al., 2013b ); in lung cancer, it restrains angiogenesis ( Yang et al., 2021 ). miR-491-5p is also reportedly expressed in placental tissue and has potential roles in trophoblast proliferation, invasion, and angiogenesis ( Liu et al., 2020a ). Compared with normal placental tissue, miR-491-5p is upregulated in placental tissue collected from patients with preeclampsia, and overexpression suppresses trophoblast invasion and vascular remodeling ( Liu et al., 2020a ).…”

“…miR-491-5p is also reportedly expressed in placental tissue and has potential roles in trophoblast proliferation, invasion, and angiogenesis ( Liu et al., 2020a ). Compared with normal placental tissue, miR-491-5p is upregulated in placental tissue collected from patients with preeclampsia, and overexpression suppresses trophoblast invasion and vascular remodeling ( Liu et al., 2020a ). Similarly, in the present study, miR-491-5p was expressed at higher levels in villous tissues from women with tubal EP compared to those with NP.…”

Expression profiles of MMP-9 and EMMPRIN in chronic rhinosinusitis with nasal polyps

“…miR-29b-3p has been found to directly target MMP-9 mRNA and that miR29b3p expression is moderately positively correlated with the expression of MMP-9 in CRSwNPs 6 . Other miRNAs that directly or indirectly affect MMP-9 expression include let-7e 7 , miR-129, miR-335 8 , miR-211 9 , miR-491-5p 10 and miR-1253 11 . Moreover, novel classes of ncRNAs that can regulate gene expression are tRNA-derived fragments (tRFs) and long ncRNAs 12 , 13 , whose role in the pathogenesis of CRSwNP remains to be elucidated.…”

Therapeutic aspect of microRNA inhibition in various types of hypertension and hypertensive complications

“…These findings suggested that miR-491-5p could be a promising therapeutic target for treating PE. However, the study has shown limitations that miR-491-5p expression levels were only examined in placental tissues taken from pregnant women undergoing caesarean sections, implying that its expression levels may not be ideal for prenatal screening of PE patients (Liu et al, 2020). In 2021, Wang et al, studies revealed that the transcriptional levels of miR-155 in the placenta were higher among patients with PE than in healthy pregnant women.…”