Abstract
BACKGROUND: Exosomes are critical mediators of tumor cell-microenvironment cross talk. However, the mechanisms by which hypoxic Lung adenocarcinoma (LUAD)-derived exosomes modulate macrophage polarization remain largely unknown. The aim of this study was to investigate the effects of hypoxic LUAD-derived exosome on macrophage polarization and explore the underlying molecular mechanism. MATERIALS AND METHODS: LUAD-derived exosomes were isolated, and then confirmed by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. Internalization of exosomes in macrophages was detected by confocal microscope. Gain- and loss-of-function experiments, rescue experiments, and xenograft models were performed to uncover the underlying mechanisms of exosomal miR-1290 induced macrophage polarization in vitro and in vivo. RESULTS: miR-1290 was enriched in hypoxic LUAD cancer cell-derived exosomes and could be transferred to macrophages. Overexpression of miR-1290 in macrophages-induced polarization of M2 phenotype. Luciferase assay verified SOCS3 was the target of miR-1290. Hypoxic LUAD cell-derived exosomal miR-1290 activated the STAT3 signaling pathway by targeting SOCS3 to promote M2 macrophage polarization. CONCLUSION: Hypoxic LUAD cells generate miR-1290-rich exosomes that promote M2 polarization of macrophages. Targeting exosomal miR-1290 may provide a potential immunotherapeutic strategy for LUAD.