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DUB3 is a MAGEA3 deubiquitinase and a potential therapeutic target in hepatocellular carcinoma.
Chen, Yuanhong; Gao, Feng; He, Yan; Liu, Meijun; Quan, Yuan; Zhang, Peijing.
Afiliação
  • Chen Y; National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430074, China.
  • Gao F; National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430074, China.
  • He Y; National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430074, China.
  • Liu M; National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430074, China.
  • Quan Y; Stem Cell Laboratory, the Second Affiliated Hospital, Fujian Medical University, Quanzhou 362000, China.
  • Zhang P; National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430074, China.
iScience ; 27(3): 109181, 2024 Mar 15.
Article em En | MEDLINE | ID: mdl-38414853
ABSTRACT
Although melanoma-associated antigen A3 and A6 (MAGEA3/6)-specific tumor vaccines have shown antitumor effects in melanoma and non-small cell lung cancer (NSCLC), many cancers do not respond because MAGEA3 can promote cancer without triggering an immune response. Here, we identified DUB3 as the MAGEA3 deubiquitinase. DUB3 interacts with, deubiquitinates and stabilizes MAGEA3. Depletion of DUB3 in hepatocellular carcinoma (HCC) cells results in MAGEA3 degradation and P53-dependent growth inhibition. Moreover, DUB3 knockout attenuates HCC tumorigenesis in vivo, which can be rescued by restoration of MAGEA3. Intriguingly, pharmacological inhibition of DUB3 by palbociclib promotes degradation of MAGEA3 and inhibits tumor growth in preclinical models implanted with parental HCC cells but not with DUB3 knockout HCC cells. In patients with HCC, DUB3 is highly expressed, and its levels positively correlate with MAGEA3 levels. Taken together, DUB3 is a MAGEA3 deubiquitinase, and abrogating DUB3 enzymatic activity by palbociclib is a promising therapeutic strategy for HCC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: IScience Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: IScience Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China