m6A Modification Mediates Exosomal LINC00657 to Trigger Breast Cancer Progression Via Inducing Macrophage M2 Polarization

Background Exosome-mediated transfer of long noncoding RNAs (lncRNAs) is critical for the cell–cell crosstalk in the tumor microenvironment. Nevertheless, the role of breast cancer (BC) cell-derived exosomal lncRNA in macrophage polarization during the development of BC remains unclear. Methods The key lncRNAs carried by BC cell-derived exosomes were identified by RNA-seq. CCK-8, flow cytometry, and transwell assay were conducted to analyze the role of LINC00657 in BC cells. In addition, immunofluorescence, qRT-PCR, western blot, and MeRIP-PCR were used to evaluate the function and underlying mechanism of exosomal LINC00657 in macrophage polarization. Results LINC00657 was distinctly upregulated in BC-derived exosomes and it was associated with increased m6A methylation modification levels. In addition, the depletion of LINC00657 significantly diminished the proliferative activity, migration and invasion potential of BC cells, and it also accelerated cell apoptosis. Exosomal LINC00657 from MDA-MB-231 cells could facilitate macrophage M2 activation, thus stimulating BC development in turn. Furthermore, LINC00657 activated the TGF-β signaling pathway by sequestering miR-92b-3p in macrophages. Conclusion Exosomal LINC00657 secreted by BC cells could induce macrophage M2 activation, and these macrophages preferentially contributed to the malignant phenotype of BC cells. These results improve our understanding of BC and suggest a new therapeutic strategy for patients with BC.