MicroRNA-29c-3p participates in insulin function to modulate polycystic ovary syndrome via targeting Forkhead box O 3

Bioengineered. 2022 Feb;13(2):4361-4371. doi: 10.1080/21655979.2022.2033014.

Abstract

MicroRNAs (miRNAs) are gene expression regulators and changes in miRNA levels are associated with diabetes, insulin resistance, and inflammation, the latter two of which are characteristic of polycystic ovary syndrome (PCOS). The purpose of this study was to explore the specific mechanism in which miR-29 c-3p participated in insulin function to regulate PCOS by targeting Forkhead box O 3 (Foxo3). Peripheral blood from PCOS patients and healthy volunteers were first collected, and the expression levels of miR-29 c-3p and Foxo3 were detected by reverse transcription quantitative polymerase chain reaction or Western blot. Then human granular tumor cell line (KGN) was treated with insulin, and transfected with plasmid vectors interfering with miR-29 c-3p or Foxo3 expression. Cell proliferation was detected by Cell counting kit-8 and plate cloning, and cell apoptosis was tested by flow cytometry. In addition, PCOS rat model was established. PCOS rats were injected with plasmids vectors interfering with miR-29 c-3p or Foxo3 expression, respectively. Pathological changes in ovarian tissues of rats in each group were observed by hematoxylin-eosin staining, and serum sex hormones and glucose metabolism-related indicators were detected. Finally, via bioinformatics website, luciferase digestion report assay was detected the targeting relationship between miR-29 c-3p and Foxo3. The experimental results showed that miR-29 c-3p was down-regulated in PCOS, but Foxo3 was up-regulated. Up-regulated miR-29 c-3p or down-regulated Foxo3 promoted KGN cell proliferation, inhibited apoptosis in vitro, restored PCOS rat sex hormone levels and improved glucose metabolism in vivo. These results suggest that miR-29 c-3p is involved in insulin function to improve PCOS by targeting Foxo3.

Keywords: Forkhead box O 3; Polycystic Ovary Syndrome; insulin function; microRNA-29c-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cell Line
  • Female
  • Forkhead Box Protein O3* / genetics
  • Forkhead Box Protein O3* / metabolism
  • Humans
  • Insulin* / genetics
  • Insulin* / metabolism
  • MicroRNAs / blood
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Polycystic Ovary Syndrome* / genetics
  • Polycystic Ovary Syndrome* / metabolism
  • Rats

Substances

  • FOXO3 protein, human
  • FOXO3 protein, rat
  • Forkhead Box Protein O3
  • Insulin
  • MIRN29 microRNA, rat
  • MIRN29C microRNA, human
  • MicroRNAs

Grants and funding

The role and mechanism of CircRNA4779/miR-126/miR-762 axis in regulating the immune microenvironment of gastric cancer stem cells to promote gastric cancer metastasis. (No. 81760524).