MiR-383-5p promotes apoptosis of ovarian granulosa cells by targeting CIRP through the PI3K/AKT signaling pathway

Arch Gynecol Obstet. 2022 Aug;306(2):501-512. doi: 10.1007/s00404-022-06461-z. Epub 2022 Feb 28.

Abstract

Purpose: To detect miR-383-5p and cold-inducible RNA binding protein (CIRBP, CIRP) expression in patients with polycystic ovary syndrome (PCOS) and explore the mechanism underlying their effect on apoptosis in ovarian granulosa cells (GCs).

Methods: GCs were extracted from follicular fluid from 101 patients. MiR-383-5p and CIRP expression were assessed by quantitative real time polymerase chain reaction analysis. Correlation between them was assessed by Spearman correlation analysis. The potential of using miR-383-5p expression for discriminating PCOS and non-PCOS patients was predicted by receiver operating characteristic curve analysis. Proliferation and apoptosis of KGN cells transfected for miR-383-5p overexpression or knockdown was evaluated using cell counting kit-8 assay, flow cytometry, and western blot analysis. CIRP was identified as a direct target of miR-383-5p, and verified by dual-luciferase reporter assay.

Results: The expression level of miR-383-5p was decreased and CIRP mRNA was increased in PCOS patients. The expression of miR-383-5p was correlated negatively with body-mass index, basal luteinizing hormone and testosterone levels, luteinizing hormone/follicle-stimulating hormone ratio, and the number of retrieved and metaphase II oocytes. MiR-383-5p had sufficient potential for prediction of PCOS. There was a negative correlation between the expression of miR-383-5p and CIRP. Overexpression of miR-383-5p enhanced the apoptosis of KGN cells. CIRP reversed the effect of miR-383-5p on promotion of apoptosis. MiR-383-5p mimics could suppress the PI3K/AKT signaling pathway, which was activated by the CIRP overexpressing plasmid.

Conclusions: MiR-383-5p promoted apoptosis of ovarian GCs through the PI3K/AKT signaling pathway by targeting CIRP.

Keywords: Apoptosis; CIRP; Ovarian granulosa cells; PCOS; miR-383-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Proliferation
  • Female
  • Granulosa Cells* / metabolism
  • Humans
  • Luteinizing Hormone / metabolism
  • MicroRNAs* / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Polycystic Ovary Syndrome* / genetics
  • Polycystic Ovary Syndrome* / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA-Binding Proteins* / metabolism
  • Signal Transduction

Substances

  • CIRBP protein, human
  • MIRN383 microRNA, human
  • MicroRNAs
  • RNA-Binding Proteins
  • Luteinizing Hormone
  • Proto-Oncogene Proteins c-akt