Circ_0003340 regulates the expression of ENAH to affect the development of esophageal cancer through miR‐874‐3p

Abstract

AbstractBackgroundEsophageal cancer is a malignant tumor with a poor prognosis and high incidence. Circular RNAs (circRNAs) have been shown to be involved in the pathogenesis of cancers, including esophageal cancer. Here, we explored the precise role of circ_0003340 in esophageal cancer development.MethodsThe expression levels of circ_0003340, miR‐874‐3p and enabled homolog (ENAH) were detected by quantitative real‐time polymerase chain reaction and western blot. Subcellular localization and RNase R assays were used to characterize circ_0003340. Cell Counting Kit 8, flow cytometry, transwell assays were used to analyze cell proliferation, apoptosis, migration and invasion. The effect of circ_0003340 on tumor growth was assessed by tumor experiments in vivo. Dual‐luciferase reporter assay was used to analyze the relationship between miR‐874‐3p and circ_0003340 or ENAH.ResultsCirc_0003340 was mainly located in the cytoplasm and was upregulated in esophageal cancer tissues and cells. Circ_0003340 knockdown inhibited cell proliferation, migration, invasion, glucose consumption, and lactate production and induced cell apoptosis in esophageal cancer cells. Moreover, circ_0003340 knockdown suppressed tumor growth in vivo. MiR‐874‐3p was reduced in esophageal cancer tissues and cells, and it was a molecular mediator of circ_0003340 function in esophageal cancer cells. ENAH was identified as a direct and functional target of miR‐874‐3p in esophageal cancer cells. The promotion effect of circ_0003340 on ENAH was ameliorated by miR‐874‐3p.ConclusionThe data demonstrated that circ_0003340 promoted the progression of esophageal cancer through miR‐874‐3p/ENAH axis, which might provide novel therapeutic targets for esophageal cancer intervention.