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The deubiquitinase OTUB1 fosters papillary thyroid carcinoma growth through EYA1 stabilization |
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| Authors: | Peiyi Xie Qing Chao Jiuang Mao Yue Liu Jiayu Fang Jing Xie Jing Zhen Yongqi Ding Bidong Fu Yun Ke Da Huang |
| Affiliation: | 1. Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China Contribution: Investigation (lead), Software (equal), Writing - original draft (lead);2. Second College of Clinical Medicine, Zunyi Medical University, Zhuhai, China Contribution: Formal analysis (equal), Investigation (equal), Methodology (equal);3. Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, China Contribution: Investigation (equal), Software (equal);4. Second College of Clinical Medicine, Nanchang University, Nanchang, China Contribution: Formal analysis (equal), Investigation (equal), Methodology (equal);5. Second College of Clinical Medicine, Nanchang University, Nanchang, China Contribution: Methodology (equal);6. Second College of Clinical Medicine, Nanchang University, Nanchang, China Contribution: Investigation (equal);7. Second College of Clinical Medicine, Nanchang University, Nanchang, China;8. Second College of Clinical Medicine, Nanchang University, Nanchang, China Contribution: Formal analysis (equal), Investigation (equal);9. Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China |
| Abstract: | Deubiquitinating enzyme OTU domain-containing ubiquitin aldehyde-binding proteins 1 (OTUB1) has been shown to have an essential role in multiple carcinomas. However, the function of OTUB1 in papillary thyroid cancer (PTC) and the underlying mechanisms regulating PTC cells proliferation remain poorly understood. In this study, OTUB1 was significantly upregulated in papillary thyroid carcinoma tissues and cells. Through in vitro and in vivo experiments, knockdown of OTUB1 suppressed PTC cells growth whereas OTUB1 overexpression enhanced the proliferation ability of PTC cells. Moreover, the eyes absent homologue 1 (EYA1) was recognized as a potential target of OTUB1 through mass spectrometry analysis, and we further verified that EYA1 protein level was positively correlated with OTUB1 expression in PTC cells and clinical samples. Mechanistically, OTUB1 could interact with EYA1 directly and deubiquitinate EYA1 to stabilize it. At last, EYA1 was found to play an essential role in OTUB1-derived PTC cells growth. Overall, our investigation reveals that OTUB1 is a previously unrecognized oncogenic factor in PTC cells proliferation and suggests that OTUB1 might be a novel therapeutic target in PTC. |
| Keywords: | deubiquitylation EYA1 OTUB1 papillary thyroid cancer proliferation |