Circ_0000518 contributes to breast cancer development depending on the regulation of miR-1258/ZEB1 axis

Abstract

Breast cancer (BC) is a common malignancy in women. We aimed to investigate the role of circular RNA_0000518 (circRNA_0000518) in BC progression and its associated mechanism. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were utilized to measure RNA and protein expression. Cell proliferation was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay. Transwell assays were conducted to analyze cell motility. Intermolecular interaction was verified via dual-luciferase reporter assay and RNA-pull down assay. Circ_0000518 expression was up-regulated in BC tissues and cell lines. Circ_0000518 interference suppressed the proliferation, migration, invasion and glycolytic metabolism and promoted the apoptosis of BC cells. Circ_0000518 acted as a molecular sponge for microRNA-1258 (miR-1258), and circ_0000518 interference-mediated effects in BC cells were largely alleviated by the addition of anti-miR-1258. MiR-1258 interacted with the 3 untranslated region (3 UTR) of zinc finger E-box binding homeobox 1 (ZEB1) in BC cells, and miR-1258 suppressed the malignant behaviors of BC cells partly through down-regulating ZEB1. Circ_0000518 interference significantly suppressed the growth of xenograft tumors in vivo. Circ_0000518/miR-1258/ZEB1 signaling cascade was identified in this study for the first time. Circ_0000518 contributed to BC progression by binding to miR-1258 to induce ZEB1 expression.