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

Abstract

Esophageal 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. The 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. Circ_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. The 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.