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Potential role of microRNA-424 in regulating ERRγ to suppress trophoblast proliferation and invasion in fetal growth restriction

Abnormal expression of estrogen-related receptor γ (ERRγ) protein is associated with fetal growth restriction (FGR). The upstream regulators of ERRγ are still unknown. To evaluate the placental expression level of microRNA-424 (miR-424) and to demonstrate the relationship between miR-424 and FGR. Th...

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Published in:Placenta (Eastbourne) 2019-08, Vol.83, p.57-62
Main Authors: Zou, Zhiyong, He, Zhiming, Cai, Jian, Huang, Linhuan, Zhu, Hui, Luo, Yanmin
Format: Article
Language:English
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Summary:Abnormal expression of estrogen-related receptor γ (ERRγ) protein is associated with fetal growth restriction (FGR). The upstream regulators of ERRγ are still unknown. To evaluate the placental expression level of microRNA-424 (miR-424) and to demonstrate the relationship between miR-424 and FGR. The expression levels of miR-424 were detected in FGR and control placentas. HTR-8/SVneo cells were transfected with mimics or inhibitors to increase or decrease the miR-424 expression level, respectively. The transwell and CCK-8 assays were used to determine trophoblast-derived cell line invasion and proliferation. The expression levels of miR-424, ERRγ, and 17 beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) were detected by qRT-PCR and Western blotting. The relationship between miR-424, ERRγ, and HSD17B1 was determined by luciferase reporter assay. Compared to the normal pregnancy group, FGR placental tissues showed a significantly higher expression level of miR-424. The up-regulation of miR-424 decreased trophoblast-derived cell line invasion and proliferation. Down-regulation of miR-424 enhanced invasive and proliferative abilities of the cell lines. Over-expression of miR-424 reduced ERRγ protein levels and decreased both mRNA and protein levels of HSD17B1. Thus down-regulation of miR-424 induced protein expression of ERRγ and enhanced the mRNA and protein expressions of HSD17B1. MiR-424 probably mediated the expression of ERRγ via binding to sites other than mRNA 3′UTR. MiR-424 may be associated with the pathogenesis of FGR by modulating trophoblast-derived cell line proliferation and invasion. MiR-424 may play a role in mediating the protein expressions of ERRγ and HSD17B1. •MiR-424 may be associated with the pathogenesis of fetal growth restriction.•MiR-424 may play a role in mediating the protein expressions of ERRγ and HSD17B1.•miR-424 can modulate the proliferation and invasion of trophoblast derived cell line.
ISSN:0143-4004
1532-3102
DOI:10.1016/j.placenta.2019.07.001