Dysregulation of miR-202-3p Affects Migration and Invasion of Endometrial Stromal Cells in Endometriosis via Targeting ROCK1

Reprod Sci. 2020 Feb;27(2):731-742. doi: 10.1007/s43032-019-00079-4. Epub 2020 Jan 6.

Abstract

Dysregulation of microRNAs in endometrial cells plays a pivotal role in the pathogenesis of endometriosis (EM). This study aims to investigate the implication of aberrant miR-202-3p expression in EM and the underlying mechanisms. We demonstrated that miR-202-3p was significantly downregulated in eutopic endometrium of EM in comparison to normal endometrial samples (P < 0.05). Primary endometrial stromal cells (ESCs) isolated from eutopic or ectopic endometrium also showed a significant decrease in miR-202-3p level compared to ESCs from normal endometrium (P < 0.01). Functional studies using MTT, wound healing assay and transwell assay indicated that overexpression of miR-202-3p greatly impaired cell viability, migration, and invasion, whereas suppression of miR-202-3p exhibited the opposite effects (P < 0.05 or P < 0.01). miR-202-3p mimics or inhibitors transfection significantly decreased or increased expression of Rho-associated, coiled-coil containing protein kinase 1 (ROCK1), respectively, in ESCs (P < 0.01). Using dual luciferase reporter assay, we validated ROCK1 as a direct target of miR-202-3p. Moreover, negative correlations between miR-202-3p and ROCK1 mRNA/protein levels were determined in both eutopic and normal control endometrium (P < 0.01). In conclusion, these findings suggest that suppression of miR-202-3p in ESCs results in enhanced cell viability, invasion, and migration at least partially via upregulation of its target ROCK1, which eventually contributes to the development of endometriosis.

Keywords: Endometrial stromal cell; Endometriosis; ROCK1; miR-202-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Movement*
  • Cell Survival
  • Cells, Cultured
  • Endometriosis / metabolism*
  • Endometrium / metabolism*
  • Female
  • Humans
  • MicroRNAs / metabolism*
  • Stromal Cells / metabolism*
  • rho-Associated Kinases / metabolism*

Substances

  • MIRN202 microRNA, human
  • MicroRNAs
  • ROCK1 protein, human
  • rho-Associated Kinases