• SMG-1 is overexpressed in HNSCC tissues compared to normal counterparts, suggesting a potential oncogenic role.
• SMG-1 knockdown does not affect HNSCC cell proliferation or tumor growth in vitro and in vivo, indicating a non-essential role in tumor progression.
• SMG-1 expression status does not correlate with overall survival in radiotherapy-naïve HNSCC patients, but SMG-1 knockdown enhances radiosensitivity in vitro.
• SMG-1 may serve as a prognostic indicator for radiotherapy response in HNSCC, warranting further clinical validation.