{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Pornour M"],"funding":["BLRD VA","HHS | NIH | National Cancer Institute","U.S. Department of Defense (DOD)","U.S. Department of Defense","NCI NIH HHS","HHS | NIH | National Cancer Institute (NCI)","NIGMS NIH HHS"],"pagination":["e2403331121"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11295044"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["121(31)"],"pubmed_abstract":["Androgen receptor (AR) is a main driver for castration-resistant prostate cancer (CRPC). c-Myc is an oncogene underlying prostate tumorigenesis. Here, we find that the deubiquitinase USP11 targets both AR and c-Myc in prostate cancer (PCa). USP11 expression was up-regulated in metastatic PCa and CRPC. USP11 knockdown (KD) significantly inhibited PCa cell growth. Our RNA-seq studies revealed AR and c-Myc as the top transcription factors altered after USP11 KD. ChIP-seq analysis showed that either USP11 KD or replacement of endogenous USP11 with a catalytic-inactive USP11 mutant significantly decreased chromatin binding by AR and c-Myc. We find that USP11 employs two mechanisms to up-regulate AR and c-Myc levels: namely, deubiquitination of AR and c-Myc proteins to increase their stability and deubiquitination of H2A-K119Ub, a repressive histone mark, on promoters of AR and c-Myc genes to increase their transcription. AR and c-Myc reexpression in USP11-KD PCa cells partly rescued cell growth defects. Thus, our studies reveal a tumor-promoting role for USP11 in aggressive PCa through upregulation of AR and c-Myc activities and support USP11 as a potential target against PCa."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["USP11 promotes prostate cancer progression by up-regulating AR and c-Myc activity."],"pmcid":["PMC11295044"],"funding_grant_id":["R01 GM129468","R01 CA244667","PC210437","P30 CA134274","I01 BX000545","R01CA244667"],"pubmed_authors":["Hussain A","Jeon HY","Qi J","Dong X","Xu R","Gleave M","Ryu H","Chen H","Pornour M","Zhuang Z","Khadka S","Barbieri C","Lam HM","Wang Q","Oo HZ"],"additional_accession":[]},"is_claimable":false,"name":"USP11 promotes prostate cancer progression by up-regulating AR and c-Myc activity.","description":"Androgen receptor (AR) is a main driver for castration-resistant prostate cancer (CRPC). c-Myc is an oncogene underlying prostate tumorigenesis. Here, we find that the deubiquitinase USP11 targets both AR and c-Myc in prostate cancer (PCa). USP11 expression was up-regulated in metastatic PCa and CRPC. USP11 knockdown (KD) significantly inhibited PCa cell growth. Our RNA-seq studies revealed AR and c-Myc as the top transcription factors altered after USP11 KD. ChIP-seq analysis showed that either USP11 KD or replacement of endogenous USP11 with a catalytic-inactive USP11 mutant significantly decreased chromatin binding by AR and c-Myc. We find that USP11 employs two mechanisms to up-regulate AR and c-Myc levels: namely, deubiquitination of AR and c-Myc proteins to increase their stability and deubiquitination of H2A-K119Ub, a repressive histone mark, on promoters of AR and c-Myc genes to increase their transcription. AR and c-Myc reexpression in USP11-KD PCa cells partly rescued cell growth defects. Thus, our studies reveal a tumor-promoting role for USP11 in aggressive PCa through upregulation of AR and c-Myc activities and support USP11 as a potential target against PCa.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jul","modification":"2025-04-04T02:09:53.34Z","creation":"2025-04-04T02:09:53.34Z"},"accession":"S-EPMC11295044","cross_references":{"pubmed":["39052835"],"doi":["10.1073/pnas.2403331121"]}}