TY - JOUR
T1 - Prostate-specific oncogene OTUD6A promotes prostatic tumorigenesis via deubiquitinating and stabilizing c-Myc
AU - Peng, Yunhua
AU - Liu, Jing
AU - Wang, Zhen
AU - Cui, Chunping
AU - Zhang, Tiantian
AU - Zhang, Shuangxi
AU - Gao, Peipei
AU - Hou, Zhanwu
AU - Liu, Huadong
AU - Guo, Jianping
AU - Zhang, Jinfang
AU - Wen, Yurong
AU - Wei, Wenyi
AU - Zhang, Lingqiang
AU - Liu, Jiankang
AU - Long, Jiangang
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.
PY - 2022/9
Y1 - 2022/9
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85125242303
U2 - 10.1038/s41418-022-00960-x
DO - 10.1038/s41418-022-00960-x
M3 - 文章
C2 - 35217790
AN - SCOPUS:85125242303
SN - 1350-9047
VL - 29
SP - 1730
EP - 1743
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 9
ER -
