泛素化是一个可逆的过程，不仅控制蛋白质的合成和降解，而且对蛋白质的转运、定位和生物活性也至关重要。去泛素化酶（DUB）功能失调导致多种疾病，包括癌症。本研究旨在探索关键DUB在头颈鳞状细胞癌（HNSCC）中的功能和机制。通过生物信息学分析和免疫组化检测，发现与癌旁正常组织相比，YOD1在HNSCC标本中显著下调。进一步分析揭示了YOD1表达降低与HNSCC的恶性进展以及不良预后有关。体内外实验结果验证了YOD1消耗显著促进了HNSCC的生长、侵袭和上皮间质转化。机制上，YOD1通过抑制TRIM33的泛素化和降解抑制了ERK/β-连环蛋白途径的激活，从而限制了HNSCC的进展。总体而言，我们的研究发现了YOD1在肿瘤进展中的分子机制，并为HNSCC治疗提供了一个新的潜在治疗靶点。© 2023. 作者。

Ubiquitination is a reversible process that not only controls protein synthesis and degradation, but also is essential for protein transport, localization and biological activity. Deubiquitinating enzyme (DUB) dysfunction leads to various diseases, including cancer. In this study, we aimed to explore the functions and mechanisms of crucial DUBs in head and neck squamous cell carcinoma (HNSCC). Based on bioinformatic analysis and immunohistochemistry detection, YOD1 was identified to be significantly downregulated in HNSCC specimens compared with adjacent normal tissues. Further analysis revealed that reduced YOD1 expression was associated with the malignant progression of HNSCC and indicated poor prognosis. The results of the in vitro and in vivo experiments verified that YOD1 depletion significantly promoted growth, invasion, and epithelial-mesenchymal transition in HNSCC. Mechanistically, YOD1 inhibited the activation of the ERK/β-catenin pathway by suppressing the ubiquitination and degradation of TRIM33, leading to the constriction of HNSCC progression. Overall, our findings reveal the molecular mechanism underlying the role of YOD1 in tumor progression and provide a novel potential therapeutic target for HNSCC treatment.© 2023. The Author(s).