CircRNA FGFR3 induces epithelial-mesenchymal transition of ovarian cancer by regulating miR-29a-3p/E2F1 axis

Aging (Albany NY). 2020 Jul 15;12(14):14080-14091. doi: 10.18632/aging.103388. Epub 2020 Jul 15.

Abstract

Circular RNAs (circRNAs) are a class of non-coding RNAs that regulate gene expression after transcription. However, the specific function of circRNAs in ovarian cancer remains undetermined. Previous studies have demonstrated abnormal expression of circFGFR3 in several cancers. The present study was designed to reveal the roles of circFGFR3 in ovarian cancer (OC). CircFGFR3 expression in OC tissues and cells was detected by RT-qPCR. The effects of CircFGFR3 on OC cells were evaluated by transwell assay and CCK-8 assay. Finally, the underlying mechanism was further revealed by luciferase reporter assay and western blotting. Our results showed that circFGFR3 expression was higher in OC cells and tissues than in normal ovarian cells and adjacent normal tissues; in addition, in OC patients, a high level of CircFGFR3 was related to lower survival rates and higher recurrence rates than a low level of circFGFR3. CircFGFR3 overexpression promotes OC progression by inducing epithelial-mesenchymal transition (EMT) in vitro. Mechanistically, circFGFR3 upregulates E2F1 expression by sponging miR-29a-3p, and the overexpression of E2F1 or the suppression of miR-29a-3p induces OC cell EMT. Therefore, circFGFR3 serves as a promoter of OC by inducing OC cell EMT via the miR-29a-3p/E2F1 axis and circFGFR3 may be a prognostic biomarker for OC patients.

Keywords: E2F1; EMT; circFGFR3; ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cell Line, Tumor
  • E2F1 Transcription Factor / genetics*
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Knockdown Techniques
  • Humans
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology
  • Neoplasm Recurrence, Local / genetics
  • Ovarian Neoplasms / genetics*
  • Prognosis
  • RNA, Circular / genetics*
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics*
  • Signal Transduction / genetics
  • Survival Rate
  • Up-Regulation / genetics

Substances

  • E2F1 Transcription Factor
  • E2F1 protein, human
  • MIRN29a microRNA, human
  • MicroRNAs
  • RNA, Circular
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3