MicroRNA-23a-3p overexpression represses proliferation and accelerates apoptosis of granular cells in polycystic ovarian syndrome by targeting HMGA2

Gynecol Endocrinol. 2023 Dec;39(1):2172155. doi: 10.1080/09513590.2023.2172155. Epub 2023 Feb 21.

Abstract

Objective: Granular cells (GCs) are involved in polycystic ovarian syndrome (PCOS) progression. MicroRNA (miR)-23a downregulation is linked to PCOS development. Therefore, this research explored the influences of miR-23a-3p on GC proliferation and apoptosis in PCOS.

Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were conducted to examine miR-23a-3p and HMGA2 expression in GCs of patients with PCOS. Then, miR-23a-3p and/or HMGA2 expression was altered in GCs (KGN and SVOG), after which miR-23a-3p, HMGA2, Wnt2, and β-catenin expression, GC viability, and GC apoptosis were measured by RT-qPCR and western blotting, MTT assay, and flow cytometry, respectively. A dual-luciferase reporter gene assay was utilized to assess the targeting relationship between miR-23a-3p and HMGA2. Finally, GC viability and apoptosis were tested after the combined treatment of miR-23a-3p mimic and pcDNA3.1-HMGA2.

Results: miR-23a-3p was poorly expressed but HMGA2 was overexpressed in GCs of patients with PCOS. Mechanistically, HMGA2 was negatively targeted by miR-23a-3p in GCs. Furthermore, miR-23a-3p inhibition or HMGA2 upregulation elevated viability and reduced apoptosis of KGN and SVOG cells, along with increased Wnt2 and β-catenin expression. In KNG cells, HMGA2 overexpression abrogated the impacts of miR-23a-3p overexpression on GC viability and apoptosis.

Conclusions: Collectively, miR-23a-3p decreased HMGA2 expression to block the Wnt/β-catenin pathway, thereby depressing viability and facilitating apoptosis of GCs.

Keywords: HMGA2; Polycystic ovarian syndrome; Proliferation; Wnt/β-catenin pathway; apoptosis; granular cells; microRNA-23a-3p.

MeSH terms

  • Apoptosis
  • Cell Proliferation
  • Female
  • HMGA2 Protein* / metabolism
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Polycystic Ovary Syndrome* / genetics
  • Polycystic Ovary Syndrome* / metabolism
  • beta Catenin / genetics

Substances

  • beta Catenin
  • MicroRNAs
  • HMGA2 Protein