EGR1 Overexpression Inhibits the Occurrence of Preeclampsia by Binding to MicroRNA-574 Promoter and Upregulating GAB1

EGR1 Overexpression Inhibits the Occurrence of Preeclampsia by Binding to MicroRNA-574 Promoter and Upregulating GAB1
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DOI:
10.1007/s43032-020-00392-3
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发表时间:
2020-11-19
影响因子:
2.9
通讯作者:
Gao, Qun
Gao, Qun
中科院分区:
医学4区
文献类型:
--
作者:
Chen, Jie;Zhan, Ying;Gao, Qun

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Early growth response protein 1 (EGR1) is potent in modulating placental trophoblast cell growth and shows a differential expression in preeclampsia (PE). We aimed to identify the downstream mechanism of EGR1 in PE. RT-qPCR showed EGR1 was significantly decreased in PE placenta. Overexpression of EGR1 facilitated the proliferation and invasion of HTR-8/Svneo cells, and reduced the concentration of human chorionic gonadotrophin (HCG) in the supernatant. Bioinformatics prediction, ChIP, and luciferase reporter experiments revealed that EGR1 inhibited miR-574 expression by binding to miR-574 promoter and that miR-574 targeted GAB1. Furthermore, overexpression of miR-574 inhibited the proliferation and invasion of HTR-8/Svneo cells. GAB1 was downregulated in placenta of PE patients, which was positively correlated with EGR1 and negatively correlated with miR-574. Inhibition of GAB1 attenuated the effect of EGR1 overexpression on the proliferation and invasion of HTR-8/Svneo cells. All in all, EGR1 upregulated GAB1 by inhibiting miR-574, thus contributing to trophoblast cell proliferation and invasion.