The deubiquitinating enzyme ATXN3 promotes the progression of anaplastic thyroid carcinoma by stabilizing EIF5A2. (1st November 2021)

• Record Type: Journal Article
• Authors: Zhuang, Shimin; Xie, Jing; Zhen, Jing; Guo, Liangyun; Hong, Zhengdong; Li, Feihong; Xu, Debin
• Is Part Of: Molecular and cellular endocrinology. Volume 537(2021)
• Publication Date: 2021-11-01
• Subjects: ATXN3 -- EIF5A2 -- ATC -- Deubiquitination -- Proliferation -- Migration; ATXN3 ataxin-3 -- ATC anaplastic thyroid carcinoma -- EIF5A2 Eukaryotic translation initiation factor 5A2; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2021.111440
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: 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. Graphical abstract: Image 1 Highlights: ATXN3 is significantly overexpressed in ATC tissues. ATXN3 accelerates ATC cell proliferation and metastasis in vivo and in vitro. ATXN3 promotes the proliferation and metastasis of ATC cells through EIF5A2. ATXN3 stabilizes EIF5A2 through deubiquitination.