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

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 0 -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.

Emerging landscape of circFNDC3B and its role in human malignancies

“…Wang et al. also proved circFNDC3B was highly expressed in ESCC ( 77 ). And through the experiments in vitro and in vivo , they confirmed the function of circFNDC3B in ESCC.…”

“…Several researches had been conducted to investigate the role of circFNDC3B in the malignant progression of esophageal cancer by Luo et al., Tang et al., and Wang et al. ( 75 – 77 ).…”

“…Based on pathological classification, esophageal carcinoma is mainly divided into squamous cell carcinoma, adenocarcinoma and other rare types (74). Several researches had been conducted to investigate the role of circFNDC3B in the malignant progression of esophageal cancer by Luo et al, Tang et al, and Wang et al (75)(76)(77).…”

Circular RNAs in Cell Cycle Regulation of Cancers

“…Interestingly, circFNDC3B and hsa_circ_00014879 (circDCAF8) positively influence the same downstream target, CDC25A. CircFNDC3B mediates the action through inhibiting miR-214-3p, whereas circDCAF8 suppresses miR-519-3p [ 125 , 126 ]. Hsa_circ_0003340 (circOGDH) was reported to absorb miR-940 and modulate its downstream target expression, protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1).…”