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

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

• Polycystic ovarian syndrome
• granular cells
• microRNA-23a-3p
• HMGA2
• Proliferation
• apoptosis