Up-regulation of miR-133a-3p promotes ovary insulin resistance on granulosa cells of obese PCOS patients via inhibiting PI3K/AKT signaling

BMC Womens Health. 2022 Oct 8;22(1):412. doi: 10.1186/s12905-022-01994-6.

Abstract

Background: MicroRNAs are a type of non-coding single-stranded RNA, which is involved in the regulation of ovary insulin resistance (IR). This study aims to explore the underlying mechanisms of miR-133a-3p regulating ovary IR in obese polycystic ovary syndrome (PCOS).

Methods: Granulosa cells (GCs) were extracted from follicular fluids of PCOS patients (obese PCOS group and non-obese PCOS group) and healthy women (control group). The expression of miR-133a-3p in GCs was detected by qRT-PCR. The targets and pathways of miR-133a-3p were predicted by bioinformatics analyses. The protein levels of PI3K, p-AKT, GLUT4, p-GSK-3β, and p-FOXO1 were measured by Western blotting.

Results: MiR-133a-3p was highly expressed in GCs from PCOS patients, especially in obese PCOS patients. The protein levels of PI3K and p-AKT was downregulated in GCs from PCOS patients. There were 11 target genes of miR-133a-3p enriching in PI3K/AKT signaling pathway. miR-133a-3p mimic downregulated the expression of PI3K, p-AKT, and GLUT4, and upregulated the protein levels of p-GSK-3β and p-FOXO1. miR-133a-3p inhibitor presented the opposite effect of miR-133a-3p mimic.

Conclusion: MiR-133a-3p promotes ovary IR on GCs of obese PCOS patients via inhibiting PI3K/AKT signaling pathway. This study lays a foundation for further research on the mechanism of ovary IR in obese PCOS patients.

Keywords: Granulosa cells; Insulin resistance; Obesity; PI3K/AKT signaling; Polycystic ovarian syndrome; miR-133a-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Glycogen Synthase Kinase 3 beta / genetics
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Glycogen Synthase Kinase 3 beta / pharmacology
  • Granulosa Cells / metabolism
  • Humans
  • Insulin Resistance*
  • MicroRNAs* / genetics
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphatidylinositol 3-Kinases / pharmacology
  • Polycystic Ovary Syndrome* / complications
  • Polycystic Ovary Syndrome* / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-akt / pharmacology
  • Signal Transduction / physiology
  • Up-Regulation

Substances

  • MicroRNAs
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt