CircAGFG1 Promotes Ovarian Cancer Progression Through the miR-409-3 p/ZEB1 Axis

Technol Cancer Res Treat. 2024 Jan-Dec:23:15330338241252423. doi: 10.1177/15330338241252423.

Abstract

Objectives: Circular RNAs (circRNAs) serve a crucial regulatory role in ovarian cancer (OC). Circular RNA ArfGAP with FG repeats 1 (circAGFG1) has been shown to be involved in promoting the progression of several cancers, containing triple-negative breast cancer, esophageal cancer and colorectal cancer. However, the function of circAGFG1 in OC is unclear.

Methods: Quantitative real-time reverse transcription PCR (RT-qPCR) was conducted to determine the expression levels of circAGFG1 and miR-409-3p. The proliferation and metastasis of cells were determined by colony formation assays, EdU assays, transwell assays and wound healing assays. In addition, a dual-luciferase reporter assay was performed to validate the mechanism between circAGFG1, miR-409-3p, and ZEB1.

Results: Our data suggested that circAGFG1 was significantly overexpressed in OC tissues compared to normal ovarian epithelial tissues. Overexpression of circAGFG1 was correlated with intraperitoneal metastasis, tumor recurrence and advanced stage. Additionally, circAGFG1 overexpression revealed a poor prognosis in OC patients. Knockdown of circAGFG1 suppressed the proliferation, invasion and migration of OC cells. Mechanistically, circAGFG1 acted as a sponge of miR-409-3p to enhance the expression level of zinc finger E-box binding homeobox 1 (ZEB1), thereby conferring OC cell proliferation, invasion and migration. Importantly, re-expression of ZEB1 effectively reversed the effects of circAGFG1 knockdown on OC cells.

Conclusions: In summary, our study indicated that circAGFG1 may act as a prognostic biomarker and potential therapeutic target for patients with OC.

Keywords: ZEB1; circAGFG1; miR-409-3p; ovarian cancer; progression.

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Cell Proliferation* / genetics
  • Disease Progression*
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • MicroRNAs* / genetics
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / metabolism
  • Ovarian Neoplasms* / mortality
  • Ovarian Neoplasms* / pathology
  • Prognosis
  • RNA, Circular* / genetics
  • Zinc Finger E-box-Binding Homeobox 1* / genetics
  • Zinc Finger E-box-Binding Homeobox 1* / metabolism

Substances

  • ZEB1 protein, human
  • MIRN409 microRNA, human