Ataxin-3 (ATXN3) is a ubiquitous deubiquitinating enzyme that plays an essential role in the carcinogenesis of numerous tumors and stabilizes the expression of substrates by deubiquitination. However, the functional role of ATXN3 in anaplastic thyroid carcinoma (ATC) remains unknown. In this research, we report that ATXN3 was overexpressed in ATC compared to that in paracancerous samples. Moreover, various gain/loss functional assays were performed to indicate that ATXN3 overexpression enhanced ATC cell proliferation and metastasis. We also found that ATXN3 and eukaryotic translation initiation factor 5A2 (EIF5A2) protein levels in ATC tissues are positively correlated, and ATXN3 promotes the proliferation and metastasis of ATC cells through EIF5A2. Mechanistically, ATXN3 promotes EIF5A2 expression by directly binding to EIF5A2 to reduce its ubiquitination and degradation. Therefore, for the first time, we clarified the role of ATXN3 in the carcinogenesis of ATC cells, which provides novel insights into potential therapeutic targets for ATC progression.

Ataxin-3 (ATXN3) 是一种普遍存在的去泛素化酶，在许多肿瘤的致癌过程中起重要作用，并通过去泛素化稳定底物的表达。然而，ATXN3 在甲状腺未分化癌 (ATC) 中的功能作用仍然未知。在这项研究中，我们报告了 ATXN3 在 ATC 中的过度表达与在癌旁样本中的相比。此外，进行了各种增益/损失功能测定以表明 ATXN3 过表达增强了 ATC 细胞增殖和转移。我们还发现ATC组织中ATXN3与真核翻译起始因子5A2（EIF5A2）蛋白水平呈正相关，ATXN3通过EIF5A2促进ATC细胞的增殖和转移。机械地，ATXN3 通过直接与 EIF5A2 结合来促进 EIF5A2 的表达，从而减少其泛素化和降解。因此，我们首次阐明了 ATXN3 在 ATC 细胞癌变中的作用，这为 ATC 进展的潜在治疗靶点提供了新的见解。