Abstract
Background: Breast cancer (BC) remains one of the most harmful malignancies in women, characterized by high heterogeneity, frequent recurrence, and metastasis. The competitive endogenous RNA (ceRNA) mechanism is crucial in tumor biology. While cuproptosis, a novel copper-induced cell death, shows therapeutic promise in BC, its ceRNA-associated regulatory network is largely unknown. This study aimed to identify and characterize a specific ceRNA axis involved in BC progression and to investigate its functional relationship with cuproptosis. Methods: To explore this, we identified a potential ceRNA axis, WT1-AS/miR-206/BCL11A in BC. Its role was investigated using copper ion and reactive oxygen species (ROS) assays to evaluate cuproptosis, functional enrichment and phenotypic analyses to assess cell proliferation and migration, and luciferase reporter assays to validate molecular interactions. Rescue experiments were further conducted to delineate functional dependencies. Results: We demonstrated that the WT1-AS/miR-206/BCL11A axis promotes BC malignancy. Suppressing BCL11A significantly increased intracellular copper levels and ROS, thereby enhancing cuproptosis. This axis was essential for driving BC cell proliferation and migration. Mechanistically, luciferase assays confirmed that the long non-coding RNA WT1-AS acts as a molecular sponge for miR-206, which in turn targets and upregulates BCL11A expression. Rescue experiments indicated that the oncogenic effects of WT1-AS are partially mediated through BCL11A. Conclusions: Our study elucidates a novel ceRNA network, the WT1-AS/miR-206/BCL11A axis, which regulates BC progression and modulates cuproptosis. These findings provide fresh insights into BC biology and highlight potential diagnostic and therapeutic targets centered on cuproptosis regulation.