The HMGA2-IMP2 Pathway Promotes Granulosa Cell Proliferation in Polycystic Ovary Syndrome

Context: The high mobility group AT hook 2 (HMGA2) gene was previously identified in a genome-wide association study as a candidate risk gene that might be related to polycystic ovary syndrome (PCOS). Whether HMGA2 contributes to promoting granulosa cell (GC) proliferation in PCOS remains unknown. Objective: We sought to determine whether HMGA2 is involved in the ovarian dysfunction of PCOS and in the mechanism of increased GC proliferation. Patients and Cells: mRNA expression was analyzed in ovarian GCs from 96 women with PCOS and 58 healthy controls. Immortalized human GCs (KGN and SVOG cells) were used for the mechanism study. Main Outcome Measures: mRNA expression in ovarian GCs was measured using quantitative RT-PCR, and KGN cells were cultured for proliferation assays after overexpression or knockdown of target genes. Protein expression analysis, luciferase assays, and RNA binding protein immunoprecipitation assays were used to confirm the mechanism study. Results: HMGA2 and IGF2 mRNA binding protein 2 (IMP2) were highly expressed in the GCs of women with PCOS, and the HMGA2/IMP2 pathway promoted GC proliferation. Cyclin D2 and SERPINE1 mRNA binding protein 1 were regulated by IMP2 and were highly expressed in women with PCOS. Conclusions: The HMGA2/IMP2 pathway was activated in women with PCOS and promoted the proliferation of GCs. This might provide new insights into the dysfunction of GCs in PCOS.