The targeting of DAPK1 with miR-190a-3p promotes autophagy in trophoblast cells

Mol Reprod Dev. 2024 Jan;91(1):e23724. doi: 10.1002/mrd.23724.

Abstract

Pre-eclampsia (PE) is a dangerous pathological status that occurs during pregnancy and is a leading reason for both maternal and fetal death. Autophagy is necessary for cellular survival in the face of environmental stress as well as cellular homeostasis and energy management. Aberrant microRNA (miRNA) expression is crucial in the pathophysiology of PE. Although studies have shown that miRNA (miR)-190a-3p function is tissue-specific, the precise involvement of miR-190a-3p in PE has yet to be determined. We discovered that miR-190a-3p was significantly lower and death-associated protein kinase 1 (DAPK1) was significantly higher in PE placental tissues compared to normal tissues, which is consistent with the results in cells. The luciferase analyses demonstrated the target-regulatory relationship between miR-190a-3p and DAPK1. The inhibitory effect of miR-190a-3p on autophagy was reversed by co-transfection of si-DAPK1 and miR-190a-3p inhibitors. Thus, our data indicate that the hypoxia-dependent miR-190a-3p/DAPK1 regulatory pathway is implicated in the development and progression of PE by promoting autophagy in trophoblast cells.

Keywords: DAPK1; autophagy; miRNA-190a-3p; trophoblast.

MeSH terms

  • Autophagy / genetics
  • Cell Movement
  • Cell Proliferation
  • Death-Associated Protein Kinases* / genetics
  • Death-Associated Protein Kinases* / metabolism
  • Female
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Placenta / metabolism
  • Pre-Eclampsia* / metabolism
  • Pregnancy
  • Trophoblasts / metabolism

Substances

  • DAPK1 protein, human
  • Death-Associated Protein Kinases
  • MicroRNAs
  • MIRN190 microRNA, human