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The Deubiquitinase USP28 Maintains the Expression of the Transcription Factor MYCN and Is Essential in Neuroblastoma Cells

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机构: [1]Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China. [2]Institute of Translational Medicine, Zhejiang University Medical School, Hangzhou, Zhejiang 310058, China. [3]Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058 China [4]Chaser Therapeutics Inc., Hangzhou, Zhejiang 310018, China [5]Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu 610000, China [6]Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu 610000, China
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Neuroblastoma (NB) is one of the most common extracranial solid tumors in children. MYCN gene amplification is highly associated with poor prognosis in high-risk neuroblastoma patients. In non-MYCN-amplified high-risk NB patients, the expression of c-MYC (MYCC) and its target genes is highly elevated. USP28 as a deubiquitinase is known to regulate the stability of MYCC. We show here USP28 also regulates the stability of MYCN. Genetic depletion or pharmacologic inhibition of the deubiquitinase strongly destabilizes MYCN and stops the growth of neuroblastoma cells that overexpress MYCN. In addition, MYCC could be similarly destabilized in non-MYCN neuroblastoma cells by compromising USP28 function. Our results strongly suggest USP28 as a therapeutic target for neuroblastoma with or without MYCN amplification/overexpression.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

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出版当年[2023]版:
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学
最新[2023]版:
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学
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出版当年[2023]版:
Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版:
Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

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第一作者机构: [1]Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China. [5]Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu 610000, China
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通讯机构: [1]Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China. [2]Institute of Translational Medicine, Zhejiang University Medical School, Hangzhou, Zhejiang 310058, China. [3]Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058 China
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