The diagnostic value and regulatory mechanism of miR-200a targeting ZEB1 in pregnancy-induced hypertension

Hypertens Pregnancy. 2020 Aug;39(3):243-251. doi: 10.1080/10641955.2020.1757700. Epub 2020 Apr 29.

Abstract

Objective: To investigate the diagnostic value and regulatory mechanism of miR-200a targeting ZEB1 in pregnancy-induced hypertension (PIH).

Methods: The expression of miR-200a and ZEB1 was detected in the placenta of PIH patients, and then the human trophoblastic cell line JEG-3 was transfected and divided into different groups: control group, NC group, ZEB1 siRNA group, miR-200a inhibitor group and miR-200a inhibitor group + ZEB1 siRNA group. After transfection, cell proliferation and migration/invasion were evaluated byMTT and Transwell assays, respectively, whereas apoptosis was assessed byflow cytometry. MiR-200a was measured by qRT-PCR, while ZEB1 was detectedby Western blotting.

Results: The expression of miR-200a was gradually increased in the placenta of patients with hypertension and mild or severe preeclampsia, while the mRNA and protein levels of ZEB1 were downregulated. A dual-luciferase reporter assay was performed to confirm the targeting relationship between miR-200a andZEB1.Compared to the control, the miR-200a inhibitor caused a strongdecrease in miR-200a andan upregulation of ZEB1, with a significant enhancement ofcell proliferation, migration and invasion and a decrease in apoptosis. However, no significant alteration was observedin the miR-200a level after administration of ZEB1 siRNA, while ZEB1 was downregulated, with significant suppression of growth.

Conclusion: MiR-200a was upregulated in PIH patients, andinhibition of miR-200a may improve disease progression, as it could facilitatetrophoblastproliferation, migration and invasionandinhibitapoptosisby targeting ZEB1.

Keywords: PIH; ZEB1; miR-200a; pregnancy-induced hypertension.

MeSH terms

  • Adult
  • Apoptosis / physiology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Disease Progression
  • Female
  • Humans
  • Hypertension, Pregnancy-Induced / diagnosis*
  • Hypertension, Pregnancy-Induced / genetics
  • Hypertension, Pregnancy-Induced / metabolism
  • MicroRNAs / metabolism*
  • Placenta / metabolism*
  • Pregnancy
  • Trophoblasts / metabolism*
  • Up-Regulation*
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism*

Substances

  • MIRN200 microRNA, human
  • MicroRNAs
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1