Non-coding RNA genes modulate PI3K/AKT signaling pathway in polycystic ovary syndrome

Mol Biol Rep. 2023 Oct;50(10):8361-8372. doi: 10.1007/s11033-023-08604-0. Epub 2023 Aug 24.


Background: The PI3K protein kinase B (PI3K/AKT) signaling pathway has crucial roles in insulin signaling and other endocrine disorders. The purpose of this study is to validate the association of PCOS with PI3K/AKT pathway target genes, miRNA486-5p, and miRNA483-5p as well as to evaluate the outcome of metformin on the pathogenesis of PCOS. METHODS: This case-controlled study included 3 subject groups: twenty healthy females (control group), twenty PCOS females before treatment, and twenty PCOS females treated with metformin at a dose (500 mg 3 times per day for 3 months). The following gene expressions were assessed by real-time PCR: PI3K, AKT, ERK, GLUT4, miRNA486-5p, and miRNA483-5p in the whole blood.

Results: There was a significant decrease in miRNA486-5p and miRNA483-5p in the PCOS group with a significant negative correlation between miRNA486-5p and PI3K and a significant negative correlation between miRNA483-5p and ERK. Metformin treatment resulted in significant elevation of the studied miRNA, significant downregulation of PI3K/AKT target genes, and significant amelioration of the gonadotrophic hormonal imbalance and insulin resistance markers: fasting blood glucose, HBA1C, fasting insulin, and GLUT4 gene expression.

Conclusions: miRNA486 and miRNA483 downregulation may contribute to the etiology of PCOS, influence glucose metabolism, and result in IR in PCOS. Metformin's upregulation of those miRNAs affects glucose metabolism by controlling the expression of GLUT4, ameliorates PCOS-related insulin resistance, and improves PCOS-related hormonal imbalance by controlling the PI3K/AKT signaling pathway.

Keywords: GLUT 4; PCOS; PI3K/AKT; miRNA 483; miRNA 486.

MeSH terms

  • Female
  • Glucose
  • Humans
  • Insulin
  • Insulin Resistance* / genetics
  • Metformin* / pharmacology
  • Metformin* / therapeutic use
  • MicroRNAs* / genetics
  • MicroRNAs* / therapeutic use
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Polycystic Ovary Syndrome* / drug therapy
  • Polycystic Ovary Syndrome* / genetics
  • Polycystic Ovary Syndrome* / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction


  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Insulin
  • MicroRNAs
  • Metformin
  • Glucose
  • MIRN483 microRNA, human
  • MIRN486 microRNA, human