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Cancer cell-derived exosomes regulate tumor growth and progression. However, the effects of exosomes and its contents on head and neck squamous cell carcinoma (HNSCC) and its underlying mechanisms remain unclear. Here, we found HNSCC displayed a dysregulation of exosomes biogenesis. miR-185-3p was one of the most upregulated exosome-derived miRNAs in HNSCC. Functional assay showed that RAB25 is a direct downstream target of miR-185-3p. miR-185-3p/RAB25 signaling controlled tumor progression and correlated with disease prognosis. Targeti