Exosomal circRNA FNDC3B promotes the progression of esophageal squamous cell carcinoma by sponging miR-490-5p and regulating thioredoxin reductase 1 expression

Abstract

ABSTRACT Exosomal circular RNAs (circRNAs) have been reported to play critical roles in esophageal squamous cell carcinoma (ESCC). We aimed to investigate the function of exosomal circRNA FNDC3B (circFNDC3B). The RNA levels and protein levels were examined using RT-qPCR and western blot (WB) assays. Colony formation and EdU assays were used to assess cell proliferative ability. Cell migratory and invasive abilities were detected by wound healing and transwell assays. Cell apoptosis was measured by flow cytometry. Glycolysis was measured using commercial kits. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) were applied to examine the morphology and size of exosomes. Dual-luciferase reporter, RIP and RNA pull-down assays assessed the interaction of miR-490-5p with circFNDC3B or thioredoxin reductase 1 (TXNRD1). Xenograft tumor model determined the role of exosomal circFNDC3B in vivo. We observed that circFNDC3B was upregulated in ESCC samples and cells, as well as ESCC-derived exosomes. CircFNDC3B could be delivered via exosomes in tumor cells, and the colony formation, proliferation, migration, invasion, glycolysis, and in vivo growth ability of recipient cells were weakened after co-incubation with exosomal circFNDC3B-knockdown donor cells. CircFNDC3B was a miR-490-5p sponge, and miR-490-5p inhibition reversed the role of exosomal circFNDC3B-downregulating in ESCC cells. TXNRD1 was a miR-490-5p target, and TXNRD1 elevation weakened the anti-cancer function of miR-490-5p upregulation in ESCC cells. CircFNDC3B mediated TXNRD1 expression by interacting with miR-490-5p. In conclusion, exosomal circFNDC3B drove ESCC progression via regulating the miR-490-5p/TXNRD1 axis. Abbreviations EC: esophageal cancer; ESCC: esophageal squamous cell carcinoma; circRNA: circular RNA; WB: western blot; TEM: transmission electron microscopy; NTA: nanoparticle tracking analysis; TXNRD1: thioredoxin reductase 1; IHC: immunohistochemistry; RT-qPCR: reverse transcription-polymerase quantitative chain reaction; GLUT1: glucose transport protein type 1; LDHA: lactate dehydrogenase A