{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:34:10Z","timestamp":1785418450085,"version":"3.56.0"},"reference-count":60,"publisher":"National Academy of Sciences","issue":"30","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92359304"],"award-info":[{"award-number":["92359304"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jiangsu Province High-Level Hospital Funds of Zhongda Hsopitial","award":["GSP-JCYJ05"],"award-info":[{"award-number":["GSP-JCYJ05"]}]},{"name":"Jiangsu Province High-Level Hospital Funds of Zhongda Hsopitial","award":["GSP-LCYJFH11"],"award-info":[{"award-number":["GSP-LCYJFH11"]}]},{"name":"China Postdoctoral Science Foundation funded project","award":["2023M730572"],"award-info":[{"award-number":["2023M730572"]}]},{"name":"Southeast University Innovation Capability Enhancement Plan for Doctoral Students","award":["CXJU _ SEU 24228"],"award-info":[{"award-number":["CXJU _ SEU 24228"]}]},{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2024ZD0535900"],"award-info":[{"award-number":["2024ZD0535900"]}]},{"name":"Open Project Fund of Anhui Provincial Key Laboratory of Immunology Fundamentals and Clinical Medicine for Chronic Diseases","award":["MBZZ202401"],"award-info":[{"award-number":["MBZZ202401"]}]},{"name":"Outstanding Young Faculty Cultivation Program","award":["YQYB2024041"],"award-info":[{"award-number":["YQYB2024041"]}]},{"name":"Bengbu Medical University Technology Transfer and Incubation Special Project","award":["2024byzh021"],"award-info":[{"award-number":["2024byzh021"]}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472825"],"award-info":[{"award-number":["82472825"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,7,28]]},"abstract":"<jats:p>Loss of major histocompatibility complex (MHC)-I is a hallmark of prostate cancer (PCa) immune evasion and immunotherapy failure. Here, we identify ZNF263 as a transcriptional repressor that silences MHC-I by recruiting nucleosome-remodeling and deacetylase (NuRD) to the STAT1 promoter, reducing STAT1 and MHC-I expression. Hypoxia enhances this repression through two ZNF263 modifications: phosphorylation-driven phase separation that strengthens NuRD interaction and O-GlcNAcylation at S662 that aids STAT1 promoter binding. O-GlcNAcylation also promotes interaction with protein kinase, DNA\u2011activated catalytic subunit (PRKDC), amplifying phosphorylation. Interferon\u2011gamma (IFN\u2011\u03b3)\u2011induced MHC-I induction is augmented upon ZNF263 loss. In silico docking identified Viroptic as a Kr\u00fcppel\u2011associated box (KRAB) pocket binder disrupting ZNF263\u2013NuRD, derepressing STAT1, and potentiating IFN-\u03b3 antitumor immunity in vivo. High ZNF263 correlates with low MHC-I, scarce CD8+ T cells, and poor survival, providing rationale for targeting ZNF263 in PCa immunotherapy.<\/jats:p>","DOI":"10.1073\/pnas.2603231123","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T18:00:45Z","timestamp":1784656845000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["ZNF263\u2013NuRD-mediated repression of STAT1 curtails MHC-I antigen presentation and IFN-\u03b3 efficacy in prostate cancer"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7043-6307","authenticated-orcid":false,"given":"Han","family":"Guan","sequence":"first","affiliation":[{"name":"Department of Urology, Zhongda Hospital, School of Medicine, Southeast University","place":["Nanjing, China"]},{"name":"Department of Urology, The First Affiliated Hospital of Bengbu Medical University","place":["Bengbu, China"]},{"name":"Anhui Province Key Laboratory of Immunology in Chronic Diseases, School of Basic Medicine, Bengbu Medical University","place":["Bengbu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0816-5999","authenticated-orcid":false,"given":"Likai","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Urology, Zhongda Hospital, School of Medicine, Southeast University","place":["Nanjing, China"]},{"name":"Anhui Province Key Laboratory of Immunology in Chronic Diseases, School of Basic Medicine, Bengbu Medical University","place":["Bengbu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6579-1179","authenticated-orcid":false,"given":"Fang","family":"Fang","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Immunology in Chronic Diseases, School of Basic Medicine, Bengbu Medical University","place":["Bengbu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9451-5438","authenticated-orcid":false,"given":"Tiange","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Urology, Zhongda Hospital, School of Medicine, Southeast University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5512-7496","authenticated-orcid":false,"given":"Yifei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Urology, Zhongda Hospital, School of Medicine, Southeast University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zonghao","family":"You","sequence":"additional","affiliation":[{"name":"Department of Urology, Zhongda Hospital, School of Medicine, Southeast University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7981-7707","authenticated-orcid":false,"given":"Hao","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Research, Zhongda Hospital, School of Medicine, Southeast University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4464-1830","authenticated-orcid":false,"given":"Ruixin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Zhongda Hospital, School of Medicine, Southeast University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5763-4069","authenticated-orcid":false,"given":"Junyong","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Urology, Zhongda Hospital, School of Medicine, Southeast University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5951-4538","authenticated-orcid":false,"given":"Gao-Jun","family":"Teng","sequence":"additional","affiliation":[{"name":"Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University","place":["Nanjing, China"]},{"id":[{"id":"https:\/\/ror.org\/03ab0at74","id-type":"ROR","asserted-by":"publisher"}],"name":"Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, National Innovation Platform for Integration of Medical Engineering Education, State Key Laboratory of Digital Medical Engineering, School of Medicine, Southeast University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1427-2037","authenticated-orcid":false,"given":"Chuanjun","family":"Shu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/059gcgy73","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5041-7865","authenticated-orcid":false,"given":"Shenghong","family":"Ju","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01k3hq685","id-type":"ROR","asserted-by":"publisher"}],"name":"Nurturing Center of Jiangsu Province for State Laboratory of Artificial Intelligence Imaging and Interventional Radiology, Department of Radiology, Zhongda Hospital, Southeast University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, Zhongda Hospital, School of Medicine, Southeast University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3078-1421","authenticated-orcid":false,"given":"Wenchao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology, Zhongda Hospital, School of Medicine, Southeast University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4993-0500","authenticated-orcid":false,"given":"Bin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Urology, Zhongda Hospital, School of Medicine, Southeast University","place":["Nanjing, China"]},{"id":[{"id":"https:\/\/ror.org\/03ab0at74","id-type":"ROR","asserted-by":"publisher"}],"name":"Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, National Innovation Platform for Integration of Medical Engineering Education, State Key Laboratory of Digital Medical Engineering, School of Medicine, Southeast University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-022-00418-6"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ado7373"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52902-5"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-00243-0"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-24-0559"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-010179"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-005592"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.07.016"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2007.03.109"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(99)80301-X"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03843-6"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-72636-0"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.113771"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2023.147580"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1134\/S0026893324700079"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.802941"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.73404"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.31259"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-023-02751-1"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-1206-7"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-24-0890"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.101107"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05656"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43676-3"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08674"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.062743"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27349-7"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.217432"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00843-w"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf934"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adt9446"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-22-3950"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.11.042"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI159628"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-025-01657-2"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-59886-w"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adj8691"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-020-00613-6"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33780-1"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36325-2"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2024.12.003"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41368-023-00221-8"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-010091"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-004561"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-022-01391-6"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199243010-00008"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2016.10.022"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adl2016"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adp8166"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01900-0"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.216798"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41737-1"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2020.01.037"},{"key":"e_1_3_4_54_2","unstructured":"S. Chen Single-cell analysis reveals transcriptomic remodellings in distinct cell types that contribute to human prostate cancer progression. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE141445. Accessed 20 September 2025."},{"key":"e_1_3_4_55_2","unstructured":"Y. Ding Gene Expression Differences in Prostate Cancers between Young and Old Men. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE88808. Accessed 20 September 2025."},{"key":"e_1_3_4_56_2","unstructured":"R. Rubicz Expression of cell cycle-regulated genes and prostate cancer prognosis in a population-based cohort. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE141551. Accessed 20 September 2025."},{"key":"e_1_3_4_57_2","unstructured":"B. S. Taylor Integrative genomic profiling of human prostate cancer. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE21034. Accessed 20 September 2025."},{"key":"e_1_3_4_58_2","unstructured":"M. Lauss Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE100797. Accessed 20 September 2025."},{"key":"e_1_3_4_59_2","unstructured":"J. W. Cho Genome-wide identification of differentially methylated promoters and enhancers associated with response to anti-PD-1 therapy in non-small cell lung cancer. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE126044. Accessed 20 September 2025."},{"key":"e_1_3_4_60_2","unstructured":"A. Sinha The Proteogenomic Landscape of Curable Prostate Cancer. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE107299. Accessed 20 September 2025."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2603231123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T18:01:25Z","timestamp":1784656885000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2603231123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":60,"journal-issue":{"issue":"30","published-print":{"date-parts":[[2026,7,28]]}},"alternative-id":["10.1073\/pnas.2603231123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2603231123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]},"assertion":[{"value":"2026-01-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2603231123"}}