Prostate-specific oncogene OTUD6A promotes prostatic tumorigenesis via deubiquitinating and stabilizing c-Myc

被引：0
作者：
Yunhua Peng
Jing Liu
Zhen Wang
Chunping Cui
Tiantian Zhang
Shuangxi Zhang
Peipei Gao
Zhanwu Hou
Huadong Liu
Jianping Guo
Jinfang Zhang
Yurong Wen
Wenyi Wei
Lingqiang Zhang
Jiankang Liu
Jiangang Long
机构：
[1] Xi’an Jiaotong University,Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology
[2] Beth Israel Deaconess Medical Center,Department of Pathology
[3] Harvard Medical School,State Key Laboratory of Proteomics, Beijing Proteome Research Center
[4] National Center for Protein Sciences (Beijing),Institute of Precision Medicine, The First Affiliated Hospital
[5] Beijing Institute of Lifeomics,Medical Research Institute, School of Medicine
[6] Sun Yat-sen University,Department of Talent Highland, The First Affiliated Hospital
[7] Wuhan University,undefined
[8] Xi’an Jiaotong University,undefined
[9] University of Health and Rehabilitation Sciences,undefined
来源：
Cell Death & Differentiation | 2022年 / 29卷
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摘要：
MYC drives the tumorigenesis of human cancers, including prostate cancer (PrCa), thus deubiquitinase (DUB) that maintains high level of c-Myc oncoprotein is a rational therapeutic target. Several ubiquitin-specific protease (USP) family members of DUB have been reported to deubiquitinate c-Myc, but none of them is the physiological DUB for c-Myc in PrCa. By screening all the DUBs, here we reveal that OTUD6A is exclusively amplified and overexpressed in PrCa but not in other cancers, eliciting a prostatic-specific oncogenic role through deubiquitinating and stabilizing c-Myc oncoprotein. Moreover, genetic ablation of OTUD6A efficiently represses prostatic tumorigenesis of both human PrCa cells and the Hi-Myc transgenic PrCa mice, via reversing the metabolic remodeling caused by c-Myc overexpression in PrCa. These results indicate that OTUD6A is a physiological DUB for c-Myc in PrCa setting and specifically promotes prostatic tumorigenesis through stabilizing c-Myc oncoprotein, suggesting that OTUD6A could be a unique therapeutic target for Myc-driven PrCa.
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页码：1730 / 1743
页数：13
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