Regulatory mechanism of miR-525-5p in over-invasion of trophoblast

J Obstet Gynaecol Res. 2021 Feb;47(2):679-688. doi: 10.1111/jog.14581. Epub 2020 Dec 1.

Abstract

Aim: To investigate the mechanism of miRNA-525-5p (miR-525-5p) in regulating the invasion of trophoblast cells.

Methods: The expressions of miR-525-5p and Homeobox D10 (HOXD10) in pre-eclampsia (PE) and normal placentas were detected. Besides the expressions of miR-525-5p and HOXD10, the levels of Vimentin, N-cadherin and E-cadherin in human trophoblast (HTR)-8 cells were also measured after cell transfection. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) and Transwell assays assessed the proliferative and invasive capabilities of HTR-8 cells, respectively. Dual-luciferase reporter assay verified the targeting relationship between miR-525-5p and HOXD10.

Results: MiR-525-5p was lowly expressed and HOXD10 was highly expressed in PE placentas. MiR-525-5p inhibition or HOXD10 overexpression suppressed proliferation, invasion and epithelial-mesenchymal transition (EMT) of HTR-8 cells. MiR-525-5p overexpression or HOXD10 knockdown promoted proliferation, invasion and EMT of HTR-8 cells. HOXD10 was a downstream target of miR-525-5p. Inhibiting HOXD10 reversed the suppressive effects of miR-525-5p inhibition on proliferation, invasion and EMT of HTR-8 cells.

Conclusion: MiR-525-5p mediates the invasion of trophoblast cells by regulating HOXD10, which provides new therapeutic targets for PE treatment.

Keywords: Homeobox D10; epithelial-mesenchymal transition; invasion; miR-525-5p; proliferation; trophoblast cell.

MeSH terms

  • Cell Movement
  • Cell Proliferation
  • Female
  • Homeodomain Proteins / genetics*
  • Humans
  • MicroRNAs* / genetics
  • Placenta
  • Pre-Eclampsia* / genetics
  • Pregnancy
  • Transcription Factors / genetics*
  • Trophoblasts

Substances

  • Homeodomain Proteins
  • MIRN525 microRNA, human
  • MicroRNAs
  • Transcription Factors
  • HOXD10 protein, human