Department of Obstetrics & Gynecology, The First Affiliated Hospital of Sun Yat-Sen University, 510080, Guangzhou, People's Republic of China.
Department of Obstetrics & Gynecology, The First Affiliated Hospital of Sun Yat-Sen University, 510080, Guangzhou, People's Republic of China.
Placenta. 2019 Aug;83:57-62. doi: 10.1016/j.placenta.2019.07.001. Epub 2019 Jul 2.
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.
雌激素相关受体 γ（ERRγ）蛋白的异常表达与胎儿生长受限（FGR）有关。ERRγ 的上游调节因子尚不清楚。
评估微小 RNA-424（miR-424）在胎盘中的表达水平，并证明 miR-424 与 FGR 之间的关系。
检测 FGR 和对照组胎盘组织中 miR-424 的表达水平。用 mimics 或抑制剂转染 HTR-8/SVneo 细胞，分别增加或减少 miR-424 的表达水平。Transwell 和 CCK-8 测定用于检测滋养层衍生细胞系的侵袭和增殖。通过 qRT-PCR 和 Western blot 检测 miR-424、ERRγ 和 17β-羟类固醇脱氢酶 1 型（HSD17B1）的表达水平。通过荧光素酶报告基因检测确定 miR-424、ERRγ 和 HSD17B1 之间的关系。
与正常妊娠组相比，FGR 胎盘组织中 miR-424 的表达水平明显升高。miR-424 的上调降低了滋养层衍生细胞系的侵袭和增殖能力。miR-424 的下调增强了细胞系的侵袭和增殖能力。miR-424 的过表达降低了 ERRγ 蛋白水平，并降低了 HSD17B1 的 mRNA 和蛋白水平。因此，下调 miR-424 诱导 ERRγ 蛋白表达，并增强 HSD17B1 的 mRNA 和蛋白表达。miR-424 可能通过结合 mRNA 3'UTR 以外的位点来介导 ERRγ 的表达。
miR-424 可能通过调节滋养层衍生细胞系的增殖和侵袭与 FGR 的发病机制有关。miR-424 可能在调节 ERRγ 和 HSD17B1 的蛋白表达中发挥作用。
