Circ_0005925 Promotes Granulosa Cell Growth by Targeting MiR-324-3p to Upregulate MAP2K6 in Polycystic Ovary Syndrome

Biochem Genet. 2023 Feb;61(1):21-34. doi: 10.1007/s10528-022-10238-z. Epub 2022 Jun 11.

Abstract

Circular RNA has been reported to be involved in the development of polycystic ovary syndrome (PCOS), but the role of circ_0005925 in the progression of PCOS is unclear. The expression levels of circ_0005925, microRNA (miR)-324-3p, and MAPK kinase 6 (MAP2K6) were examined by quantitative real-time PCR. Cell proliferation and apoptosis were determined using cell counting kit 8 assay, EdU assay, colony formation assay, and flow cytometry. Western blot analysis was used to detect the protein expression of apoptosis markers and MAP2K6. RNA interaction was verified by dual-luciferase reporter assay and RNA pull-down assay. Circ_0005925 was upregulated in GCs from PCOS patients, as well as in KGN and SVOG cells. Circ_0005925 knockdown repressed GCs proliferation and promoted apoptosis. MiR-324-3p was downregulated in PCOS patients, and it was sponged by circ_0005925. The regulation of circ_0005925 knockdown on GCs growth was abolished by miR-324-3p inhibitor. MAP2K6 was targeted by miR-324-3p, and its expression was positively regulated by circ_0005925. MiR-324-3p inhibited GCs proliferation and increased apoptosis by targeting MAP2K6. Collectively, our findings suggested that circ_0005925 promoted GCs growth through miR-324-3p/MAP2K6, which provided a promising therapeutic target for PCOS.

Keywords: Circ_0005923; MAP2K6; MiR-324-3p; Polycystic ovary syndrome.

MeSH terms

  • Apoptosis
  • Cell Proliferation
  • Female
  • Granulosa Cells
  • Humans
  • MAP Kinase Kinase 6
  • MicroRNAs* / genetics
  • Mitogen-Activated Protein Kinase Kinases
  • Polycystic Ovary Syndrome* / genetics

Substances

  • Mitogen-Activated Protein Kinase Kinases
  • MicroRNAs
  • MAP2K6 protein, human
  • MAP Kinase Kinase 6
  • MIRN324 microRNA, human