1. Prostate-specific oncogene OTUD6A promotes prostatic tumorigenesis via deubiquitinating and stabilizing c-Myc
- Author
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Peng, Yunhua, Liu, Jing, Wang, Zhen, Cui, Chunping, Zhang, Tiantian, Zhang, Shuangxi, Gao, Peipei, Hou, Zhanwu, Liu, Huadong, Guo, Jianping, Zhang, Jinfang, Wen, Yurong, Wei, Wenyi, Zhang, Lingqiang, Liu, Jiankang, and Long, Jiangang
- Abstract
MYCdrives 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 OTUD6Aefficiently represses prostatic tumorigenesis of both human PrCa cells and the Hi-Myctransgenic 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.
- Published
- 2022
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