Hsa_circ_0001756, a novel biomarker, promotes breast cancer progression via miR-584-5p/TRAF6 signaling axis

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.

The Gene Expression Omnibus (GEO) database was referenced to identify differentially expressed circRNAs in BC. Quantitative real-time polymerase chain reaction (qPCR) was used to detect the expression levels of hsa_circ_0001756 in both BC tissue samples and BC-derived cell lines. The functions of hsa_circ_0001756 were investigated both in vitro and in vivo. The luciferase reporter and rescue assays were used to clarify the molecular mechanisms of hsa_circ_0001756. Receiver operating characteristic (ROC) curve was established to evaluate the clinical value of hsa_circ_0001756 as a serum biomarker, and to investigate its potential correlation with the clinical pathological characteristics of BC patients by Chi-squared test.

Hsa_circ_0001756 expression was upregulated in BC tissues and substantially correlated with tumor size and tumor-node-metastasis (TNM) stage. Knockdown (KD) of hsa_circ_0001756 markedly inhibited the malignant potential of BC both in vitro and in vivo. Mechanistically, hsa_circ_0001756 acted as a miR-584-5p sponge to regulate TRAF6 in BC cells. Serum levels of hsa_circ_0001756 were significantly higher in pre-operative BC patients than in healthy controls, fibroadenoma patients, and post-operative BC patients. Also, serum hsa_circ_0001756 was remarkably correlated with tumor size, patient age, metastasis state, and TNM stage. The combination of the traditional tumor markers carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) with hsa_circ_0001756 significantly improved the diagnostic accuracy of BC.

Our findings indicated that hsa_circ_0001756 could promote BC malignant progression through the miR-584-5p/TRAF6 signaling axis. Especially, hsa_circ_0001756 in serum holds promise as a biomarker for BC screening and diagnosis.