Circ_0001756, a novel biomarker, promotes breast cancer progression via miR-584-5p/TRAF6 signaling axis

Abstract

Abstract Purpose Circular RNAs (circRNAs) appear to exert critical functions in breast cancer (BC). The objective of this study is to explore the usefulness of circRNAs as potential diagnostic and prognostic biomarkers of BC. Methods The Gene Expression Omnibus database was referenced to identify differentially expressed circRNAs in BC. We found that circ_0001756 was associated with the malignant potential of BC. Also, the expression levels of circ_0001756 in BC tissues and cell lines were determined by real-time quantitative polymerase chain reaction analysis. The functions of circ_0001756 were investigated both in vitro and in vivo. The luciferase reporter and rescue assays were used to clarify the molecular mechanisms of circ_0001756. Additionally, the clinical value of circ_0001756 as a serum biomarker and potential correlations with the clinicopathological characteristics of BC patients were investigated. Results Circ_0001756 expression was upregulated in BC tissues and substantially correlated with tumor size and tumor-node-metastasis (TNM) stage. Knockdown of circ_0001756 markedly inhibited the malignant potential of BC both in vitro and in vivo. Mechanistically, circ_0001756 acted as a miR-584-5p sponge to regulate TRAF6 in BC cells. Serum levels of circ_0001756 were significantly higher in pre-operative BC patients than in healthy controls, fibroadenoma patients, and post-operative BC patients. Also, serum circ_0001756 was remarkably correlated with tumor size, patient age, metastasis state, and TNM stage. The combination of the traditional tumor markers carcinoembryonic antigen and cancer antigen 15 − 3 with circ_0001756 significantly improved the diagnostic accuracy of BC. Conclusion Circ_0001756 promotes the malignancy of BC through the miR-584-5p/TRAF6 signaling axis. Additionally, serum circ_0001756 is a promising biomarker for screening and diagnosis of BC.