CircFNDC3B knockdown restrains the progression of oesophageal squamous cell carcinoma through miR-214-3p/CDC25A axis

Clin Exp Pharmacol Physiol. 2022 Nov;49(11):1209-1220. doi: 10.1111/1440-1681.13707. Epub 2022 Aug 17.

Abstract

Circular RNA (circRNAs) Fibronectin Type III Domain Containing 3B (FNDC3B) (circFNDC3B) has been revealed to be involved in the progression of oesophageal squamous cell carcinoma (ESCC). Hence, the potential regulatory network of circFNDC3B in ESCC was further investigated. Levels of genes and proteins were examined by qRT-PCR and Western blot. In vitro assays were performed using colony formation assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, wound healing assay, and transwell assay. The target relationship between miR-214-3p and circFNDC3B or cell division cycle 25 homologue A (CDC25A) was verified by dual-luciferase reporter and RIP assays. In vivo assay was carried out using the xenograft nude mice model. CircFNDC3B was highly expressed in ESCC, and high circFNDC3B expression was tightly associated with poor prognosis in ESCC patients. Functionally, circFNDC3B knockdown not only suppressed ESCC cell growth, migration and invasion in vitro, but hindered ESCC tumour growth in vivo. Mechanistically, circFNDC3B acted as a sponge for miR-214-3p to up-regulate the expression of its target CDC25A. Rescue experiments showed that miR-214-3p inhibitor reversed the anticancer effects of circFNDC3B knockdown. Moreover, forced expression of miR-214-3p suppressed the malignant phenotypes mentioned above, while this condition was abolished by CDC25A overexpression. CircFNDC3B silencing restrains the tumorigenesis of oesophageal squamous cell carcinoma through miR-214-3p/CDC25A axis, which opens a new window to the development of novel therapeutic strategy for ESCC patients.

Keywords: CDC25A; circFNDC3B; miR-214-3p; oesophageal squamous cell carcinoma.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Esophageal Neoplasms* / metabolism
  • Esophageal Squamous Cell Carcinoma* / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular / genetics
  • cdc25 Phosphatases / genetics
  • cdc25 Phosphatases / metabolism

Substances

  • MIRN214 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • CDC25A protein, human
  • cdc25 Phosphatases