Background <p>Circular_RNAs (circ_RNAs) are involved in the development and progression of human malignancies, including breast cancer. Novel circ_RNAs for breast cancer remain to be further determined. This study investigates the role and mechanism of a novel circ_RNA circ_0048766 in triple-negative breast cancer (TNBC) progression.</p> Methods <p>Bioinformatics analysis was performed using the GSE165884 database to identify differentially expressed circ_RNAs. The expression of circ_0048766 was validated in various breast cancer cell lines through quantitative real-time PCR. Functional assays, including CCK-8, flow cytometry, colony formation, and Transwell assays, were conducted in BT-549 and MDA-MB-231 cells. The mechanisms involving methyltransferase-like 3 (METTL3), miR-329-3p, and C-X-C Motif Chemokine Receptor 4 (CXCR4) were examined through bioinformatics, dual-luciferase reporter assays, RNA immunoprecipitation, and RNA pull-down. In vivo studies were conducted using a nude mouse xenograft model to evaluate tumor growth and CXCR4 expression.</p> Results <p>Circ_0048766 was significantly upregulated in TNBC cell lines compared to normal breast epithelial cells. Knockdown of circ_0048766 resulted in reduced cell viability, colony formation, migration, and invasion while increasing apoptosis in BT-549 and MDA-MB-231 cells. Mechanistically, circ_0048766 was confirmed to function as a sponge for miR-329-3p. Moreover, miR-329-3p directly suppressed CXCR4 expression, and circ_0048766 regulated CXCR4 in a miR-329-3p-dependent manner. Additionally, circ_0048766 promoted epithelial-mesenchymal transition, as evidenced by its regulation of E-cadherin, N-cadherin, and Vimentin expression via miR-329-3p. MiR-329-3p inhibition or CXCR4 overexpression reversed the effects of circ_0048766 knockdown. In vivo, circ_0048766 knockdown significantly diminished tumor growth and weight, along with decreased CXCR4 levels. METTL3 was identified as an upstream regulator mediating m6A modification of circ_0048766. Functionally, METTL3 knockdown suppressed CXCR4 expression and cell proliferation, effects that were rescued by CXCR4 overexpression.</p> Conclusions <p>Circ_0048766 is a novel oncogenic circ_RNA that promotes TNBC progression through the miR-329-3p/CXCR4 signaling axis, regulated by METTL3. This study highlights the potential of targeting the METTL3/circ_0048766/miR-329-3p/CXCR4 axis as a novel therapeutic strategy for TNBC treatment.</p> Trial registration <p>Not applicable.</p>