hsa_circRNA_BECN1 acts as a ceRNA to promote polycystic ovary syndrome progression by sponging the miR-619-5p/Rab5b axis

Mol Hum Reprod. 2023 Nov 1;29(11):gaad036. doi: 10.1093/molehr/gaad036.

Abstract

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease that affects women of reproductive age. It is also a significant cause of infertility. Circular RNAs have been found to have a crucial role in the development and progression of reproductive system diseases. In this study, we focused on circ_BECN1 and aimed to investigate its role and mechanism in PCOS, providing a foundation for early diagnosis and treatment of this condition. Our findings revealed an upregulation of circ_BECN1 expression in the ovarian granulosa cells (GCs) of PCOS patients. Additionally, the silencing of circ_BECN1 resulted in inhibited proliferation and enhanced apoptosis of the human ovarian granulosa-like tumor cell line (KGN), therefore implicating circ_BECN1 in the cell cycle process. Through a dual-luciferase reporting assay, we determined that circ_BECN1 acts as a sponge for miR-619-5p and that Rab5b is the target gene of miR-619-5p. Moreover, the expression of Rab5b was found to be upregulated in the ovarian tissue of PCOS patients. Knocking down circ_BECN1 resulted in decreased Rab5b expression, which was then restored by using a miR-619-5p inhibitor. Additionally, rescue experiments demonstrated that overexpressing Rab5b reversed the effects of circ_BECN1 knockdown on cell proliferation and apoptosis in KGN cells. In summary, our findings indicate that circ_BECN1 is upregulated in PCOS GCs and promotes cell growth and cell cycle progression, and reduces cell apoptosis by modulating the miR-619-5p/Rab5b axis. Therefore, circ_BECN1 may serve as a potential therapeutic target for PCOS treatment.

Keywords: PCOS; Rab5b; hsa_circ_BECN1; miR-619-5p; ovarian granulosa cells.

MeSH terms

  • Apoptosis / genetics
  • Beclin-1 / genetics
  • Beclin-1 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Humans
  • MicroRNAs* / genetics
  • Polycystic Ovary Syndrome* / metabolism
  • RNA, Circular / genetics
  • RNA, Circular / metabolism
  • Up-Regulation

Substances

  • Beclin-1
  • BECN1 protein, human
  • MicroRNAs
  • MIRN-619 microRNA, human
  • MIRN619 microRNA, human
  • RNA, Circular
  • RAB5C protein, human