Being one of the most prevalent malignancies, breast cancer (BC) ranks the second with regard to the causes of cancer-related deaths in female [12]. BC contains four major subtypes, namely, human epidermal growth factor receptor 2 (HER2)-enriched, luminal A, luminal B, and triple-negative BC. Triple-negative breast cancer (TNBC), compared with the rest of three, is the subtype with highest aggressiveness, and its risks of recurrence and metastasis are higher than other three subtypes [41]. TNBC features the absence or underexpression of estrogen receptor (ER), HER2 and progesterone receptor (PR), accounting for about 10%− 15% of all diagnosed BC [6], [23]. Compared to non-TNBC patients, TNBC features poor prognosis and reinforced angiogenesis; its incidence rate of lung and brain metastases is higher, and its recurrence-free interval is shorter. In addition, the efficacy of endocrine or HER2-targeted therapies is low with regard to TNBC patients [32]. Radiotherapy, surgery and chemotherapy still remain to be the preferred therapeutic methods for TNBC [3], [43]. Despite the development of treatment, the survival rate of TNBC patients is still unfavorable due to the aggressiveness of TNBC. Hence, it’s urgent to explore novel therapeutic targets for the improvement of TNBC treatments.

Circular RNA (circRNA) is a class of non-coding endogenous RNA, featuring its closed circular structure [34]. In accordance with literature review, circRNAs play modulatory roles in multiple diseases [13], including TNBC. For instance, circ-HER2 improves the sensitivity of TNBC to pertuzumab, a HER2 antibody [15]; circ-ITCH regulates the cell progression of TNBC through sequestering miR-214 and miR-17 to inactivate Wnt/β-catenin pathway [30]; circ-PGAP3 facilitates the proliferative and invasive capacities of TNBC cells by modulating miR-330–3p/Myc axis [7]; circ_0091074 modulates the expression of TAZ via miR‑1297 in order to regulate the progression of TNBC cells [9]; and circUBE2D2 propels cell progression and chemoresistance in TNBC by targeting miR-512–3p/CDCA3 axis [4]. As the circRNA of our study, circ_0008784 has been found to be high-expressed in TNBC tissues. The host gene of circ_0008784, TNFRSF19 participates in the modulation of hepatocellular carcinoma (HCC) cell proliferation and epithelial-mesenchymal transition (EMT) as reported previously [5]. Moreover, the inherited variations of a p53-responsive enhancer in 13q12.12 raise the risk of lung cancer by down-regulating the expression of TNFRSF19 [24]. However, the role of circ_0008784 in TNBC has never been reported previously.

As a highly conserved signaling pathway, Wnt/β-catenin pathway was found to regulate cancer progression. Furthermore, it has been unearthed by genome-wide sequencing and gene expression profile analyses that Wnt/β-catenin pathway is mainly associated with BC development [35]. Via literature review, it was uncovered that Wnt/β-catenin pathway is correlated with the modulation of TNBC. For instance, Nek2B facilitates β-catenin stability to induce Wnt/β-catenin pathway activation to facilitate chemotherapy resistance of TNBC [25]; circRNA_069718 propels proliferative and invasive capacities in TNBC cells by inducing Wnt/β-catenin pathway activation [40]; NuSAP1 up-regulation facilitates proliferative and invasive capacities in TNBC cells by targeting Wnt/β-catenin pathway [26]; and circ-EIF6 encodes EIF6–224aa to propel the development of TNBC via induction of Wnt/β-catenin pathway activation [17]. However, the association of circ_0008784 with this pathway has never been probed previously.

In the present study, our intention was to probe into the association of circ_0008784 with Wnt/β-catenin pathway and the underlying mechanisms in TNBC. As TNBC is an aggressive tumor, it’s crucial for us to identify novel therapeutic targets for TNBC. Our findings in this study may help to improve the therapeutic methods of TNBC patients.