AS-IV inhibits the progression of ovarian cancer by targeting the circ_0124787/miR-6875-3p/IL-1β axis

Nan Fu1, Siyue Zhang2, Ziyi Xiao2

  • 1Department of Gynecologic Oncology, Cancer Hospital Affiliated to Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu 210009, China; Yili Kazakh Autonomous Prefecture Maternal and Child Health Hospital, Yili, Xinjiang 835100, China.

Abstract

Insights

Astragaloside IV (AS-IV) suppresses ovarian cancer by regulating a pathway involving circ_0124787, miR-6875-3p, and IL-1β. This mechanism reduces pro-tumorigenic γδT17 cells, highlighting a novel therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Astragaloside IV (AS-IV), a saponin from Astragalus membranaceus, exhibits anti-tumor properties.
  • Circular RNAs (circRNAs) play a role in cancer progression and are modulated by AS-IV.

Purpose of the Study:

  • To elucidate the mechanism by which AS-IV exerts anti-tumor effects in ovarian cancer.
  • To identify key circRNAs and their interactions in AS-IV's therapeutic pathway.

Main Methods:

  • Gene microarray analysis to identify differentially expressed circRNAs in ovarian cancer.
  • ELISA assays to measure IL-1β secretion.
  • Dual-luciferase reporter assays to validate circRNA-miRNA interactions.
  • Functional studies to assess the role of the circRNA-miRNA axis in AS-IV's efficacy.

Main Results:

  • Circ_0124787 was identified as a highly expressed circRNA in ovarian carcinoma.
  • Overexpression of circ_0124787 increased IL-1β secretion, promoting γδT17 cell proliferation and tumor progression.
  • Circ_0124787 functions as a competitive endogenous RNA (ceRNA) by sponging miR-6875-3p, leading to IL-1β upregulation.
  • AS-IV's anti-tumor effect is dependent on the circ_0124787/miR-6875-3p pathway.

Conclusions:

  • A novel pathway involving AS-IV, circ_0124787, miR-6875-3p, and IL-1β was identified.
  • This pathway suppresses ovarian cancer by decreasing γδT17 cell populations.
  • The findings suggest a new therapeutic strategy targeting this axis for ovarian cancer treatment.

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