Exosomal miR-182-5p from breast cancer cells reprogram tumor-associated macrophages and promote triple-negative breast cancer progression by targeting Notch1 in macrophages.

Introduction: The regulatory role of miR-182 in breast cancer malignancy and macrophage reprogramming is well established. However, the mechanisms through which miR-182 overexpression in tumor cells influences macrophage polarization remain elusive. Material and methods: After transfection with miR-182-5p mimics, inhibitors, and controls for 24 h, exosomes were extracted by differential centrifugation from transfected MDA-MB-231. Macrophages were co-cultured with these exosomes to illustrate the regulative effects of exo-miR-182-5p reprogram macrophage. Furthermore, breast cancer cells were co-cultured with exo-miR-182-5p reprogrammed M2 macrophages to demonstrate the effects of reprogrammed M2 macrophages to influence breast cancer progression. After all, these findings were validated in a cell-derived xenograft (CDX) BALB/C nude-mouse model. Results: This study demonstrated that exosome-derived miR-182-5p from triple-negative breast cancer (TNBC) cells reprograms M2 macrophage polarization through direct combination with Notch1, thereby enhancing breast cancer progression Conclusions: This study pioneers the elucidation of the feedback loop mechanism between breast cancer cells and macrophages mediated by the exosome-derived miR-182-5p/Notch1 pathway, highlighting its role in macrophage reprogramming. Although the therapeutic application of miR-182-5p inhibitors as anticancer agents remains in the early stages, targeting macrophage polarization represents a promising avenue for breast cancer therapy.