Ubiquitin-specific protease 2a promotes hepatocellular carcinoma progression via deubiquitination and stabilization of RAB1A
| العنوان: | Ubiquitin-specific protease 2a promotes hepatocellular carcinoma progression via deubiquitination and stabilization of RAB1A |
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| المؤلفون: | Junwei Huang, Jianping Gong, Bin Xiong, Xiaoling Wu, Yan Liu, Chan Qiu, Zhibo Zhao, Min Zou |
| المصدر: | Cellular Oncology. 44:329-343 |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Cancer Research, Carcinoma, Hepatocellular, Carcinogenesis, Cell, Mice, Nude, Deubiquitinating enzyme, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Ubiquitin, Cell Movement, Cell Line, Tumor, medicine, Animals, Humans, Gene silencing, Neoplasm Invasiveness, Cell Proliferation, Mice, Inbred BALB C, biology, Protein Stability, Cell growth, Chemistry, Liver Neoplasms, Ubiquitination, General Medicine, Middle Aged, Prognosis, digestive system diseases, rab1 GTP-Binding Proteins, 030104 developmental biology, medicine.anatomical_structure, Oncology, Proteasome, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Proteolysis, Disease Progression, Cancer research, biology.protein, Molecular Medicine, Female, Neoplasm Grading, Ubiquitin Thiolesterase, Protein Binding, Deubiquitination |
| الوصف: | Deubiquitination, the inverse process of ubiquitination, is catalyzed by deubiquitinases (DUBs) that remove ubiquitin from target proteins and subsequently prevent their degradation by proteasomes. Previously, deubiquitination has been found to be involved in hepatocellular carcinoma (HCC) progression. As yet, however, little is known about the exact role of deubiquitination in the development and/or progression of this type of cancer. HCC tissues and tissue microarrays were used to detect expression of the DUB ubiquitin-specific protease 2a (USP2a). The critical role of USP2a in HCC development and progression was assessed in both in vitro cell and in vivo animal models. LC-MS/MS analyses were performed to identify potential targets of USP2a in HCC cells, after which regulation of target protein stability and ubiquitin status by USP2a were investigated. We found that USP2a was significantly upregulated in HCC tissues, and that a high expression was positively associated with a poor prognosis. Subsequently, we found that USP2a silencing resulted in inhibition of HCC cell proliferation, migration and invasion, whereas exogenous USP2a overexpression resulted in the opposite effects, both in vitro and in vivo. Mechanistically, LC-MS/MS analysis revealed that RAB1A, a key regulator of the ER and Golgi vesicular transport system, serves as a potential target of USP2a in HCC cells. In addition, we found that USP2a can deubiquitinate and stabilize RAB1A and prevent its degradation, and that this process is required for inducing HCC progression by USP2a. Our data indicate that USP2a can promote HCC progression via deubiquitination and stabilization of RAB1A. This observation indicates that DUB targeting may serve as a novel approach to improve the treatment of HCC. |
| تدمد: | 2211-3436 2211-3428 |
| DOI: | 10.1007/s13402-020-00568-8 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e1c43ab7b21834e5d7c1e3d17a492bc3 https://doi.org/10.1007/s13402-020-00568-8 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....e1c43ab7b21834e5d7c1e3d17a492bc3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22113436 22113428 |
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| DOI: | 10.1007/s13402-020-00568-8 |