Circ_FNDC3B Promotes Cell Proliferation and Metastasis in Esophageal Squamous Cell Carcinoma via Regulating MAPK1 by Binding to miR-136-5p

Biochem Genet. 2024 Jan 16. doi: 10.1007/s10528-023-10585-5. Online ahead of print.

Abstract

A handful of circular RNAs (circRNAs) associated with cancer progression have been indicated in esophageal squamous cell carcinoma (ESCC). The current study aimed to investigate the functional mechanism of circular RNA Fibronectin type III domain containing 3B (circ_FNDC3B) in ESCC. Circ_FNDC3B, FNDC3B, microRNA-136-5p (miR-136-5p) and mitogen-activated protein kinase 1 (MAPK1) were examined via the quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) and colony formation assays. Transwell assay was performed to measure cell migration and invasion. Protein analysis was implemented by western blot. Cell apoptosis was assessed via flow cytometry. Target interaction was affirmed using dual-luciferase reporter assay. The function analysis of circ_FNDC3B in vivo was explored by xenograft models. The upregulation of circ_FNDC3B was detected in ESCC tissues and cells. Functionally, ESCC cell proliferation and metastasis were repressed but apoptosis was promoted by circ_FNDC3B knockdown. Besides, circ_FNDC3B silence inhibited ESCC progression through MAPK1 downregulation. Further target analysis identified miR-136-5p as a target of circ_FNDC3B and an upstream control of MAPK1. Additionally, the regulation of si-circ_FNDC3B in ESCC was also dependent on targeting miR-136-5p. Moreover, circ_FNDC3B targeted miR-136-5p to affect MAPK1 level. Tumorigenesis in vivo was also suppressed by downregulating circ_FNDC3B to regulate miR-136-5p/MAPK1 axis. Circ_FNDC3B downregulation impeded the development of ESCC via the mediation of miR-136-5p/MAPK1 axis. This report afforded a novel insight into the functional mechanism of circ_FNDC3B in ESCC.

Keywords: Circ_FNDC3B; Esophageal squamous cell carcinoma; MAPK1; miR-136-5p.