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• W3131719466 abstract "The mechanisms underlying the hypoxic cancer cell-mediated differentiation of cancer-associated fibroblasts (CAFs) have not been elucidated yet. The present study showed that the hypoxic head and neck squamous cell carcinoma (HNSCC) cells promoted CAF-like differentiation through secreting TGF-β and small extracellular vesicles (sEVs) that contain enhanced levels of miR-192/215 family miRNAs. Caveolin-1 ( CAV1 ), which is a target gene of miR-192/215, inhibited the TGF-β/SMAD signaling and promoted CAF-like differentiation of the fibroblasts. Restoring the levels of CAV1 inhibited the hypoxic sEV- and TGF-β-induced CAF-like differentiation. The enhanced levels of miR-192/215 encapsulated in the HNSCC tissue-derived sEVs (but not serum-derived sEVs) indicated hypoxic and aggressive cancer stroma. miR-215 in the tumor tissue-derived sEVs (but not circulating sEVs) was correlated with poor overall survival of patients with HNSCC. This study demonstrated that sEVs function as a “courier” to deliver miRNAs from the cancer cells to the fibroblasts, which promotes the remodeling of the hypoxic tumor microenvironment, and that cancer tissue-derived sEV could potentially serve as a source of biomarker. • TGF-β and sEVs synergistically mediate hypoxic HNSCC cell-induced CAF-like differentiation. • HIF-1α and NF-κB dependent upregulation of miR-192/215 contributes to sEV-induced CAF-like differentiation. • The miR-192/215 target gene, CAV1, is involved in the regulation of TGF-β/SMAD signaling. • Tissue- but not serum-derived sEV miR-215 indicates aggressive hypoxic cancer stroma and poor outcome of HNSCC patients." @default.
• W3131719466 created "2021-03-01" @default.
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• W3131719466 date "2021-05-01" @default.
• W3131719466 modified "2023-09-30" @default.
• W3131719466 title "Small extracellular vesicles containing miR-192/215 mediate hypoxia-induced cancer-associated fibroblast development in head and neck squamous cell carcinoma" @default.
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• W3131719466 doi "https://doi.org/10.1016/j.canlet.2021.01.006" @default.
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