{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T14:06:47Z","timestamp":1789135607041,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372682"],"award-info":[{"award-number":["82372682"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073372"],"award-info":[{"award-number":["82073372"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Isocitrate dehydrogenase 3 alpha (IDH3A) is a key rate\u2010limiting enzyme in the tricarboxylic acid (TCA) cycle, traditionally associated with cellular energy metabolism. However, its role in cancer remains incompletely understood. Here, we demonstrate that IDH3A is significantly overexpressed in melanoma, primarily due to DNA copy number amplification. Metabolomic analysis revealed that IDH3A overexpression enhanced multiple biosynthetic intermediates, including G6P, F6P, DHAP, and 6\u2010phosphogluconate, indicating metabolic reprogramming toward anabolic processes without significantly affecting ATP or lactate production. Intriguingly, IDH3A localizes to the nucleus in melanoma cells and promotes tumorigenesis independent of its dehydrogenase activity. Nuclear IDH3A interacts with transcription factor YBX1, enriching at promoter regions of oncogenes such as\u00a0c\u2010FOS\u00a0and\u00a0c\u2010JUN, thereby suppressing apoptosis and promoting tumor growth. Furthermore, we identify NONO as a nuclear chaperone that facilitates the nuclear localization of IDH3A through direct interaction, primarily involving NONO amino acids Q166 and S207. Disruption of NONO impairs IDH3A nuclear translocation and mitigates its tumor\u2010promoting function. Collectively, our findings uncover a noncanonical role of IDH3A as a nuclear regulator of transcription via YBX1, offering novel insight into metabolic enzyme reprogramming in melanoma.<\/jats:p>","DOI":"10.1002\/advs.77762","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:14:05Z","timestamp":1789132445000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nuclear IDH3A Drives Transcriptional Programs in Melanoma via the YBX1\u2013JUN\/FOS Axis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3350-9636","authenticated-orcid":false,"given":"Juan","family":"Ran","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanchun","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Pathology Nantong Haimen District People's Hospital Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4260-4060","authenticated-orcid":false,"given":"Shengming","family":"Ruan","sequence":"additional","affiliation":[{"name":"School of Life Sciences Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juling","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Sciences Anhui Medical University  Hefei China"},{"name":"Chongqing Banan Traditional Chinese Medicine Hospital  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3920-1032","authenticated-orcid":false,"given":"Songbai","family":"Liu","sequence":"additional","affiliation":[{"name":"Jiangsu Province Engineering Research Center of Molecular Target Therapy and Companion Diagnostics in Oncology Suzhou Vocational Health College  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Mao","sequence":"additional","affiliation":[{"name":"Hefei Kingmed Medical Laboratory  Hefei Anhui China"},{"name":"School of Biological Sciences and Medical Engineering Southeast University  Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Pathology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology Nantong Haimen District People's Hospital Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2376-4712","authenticated-orcid":false,"given":"Zi","family":"Ye","sequence":"additional","affiliation":[{"name":"Institute of Hydrobiology Chinese Academy of Sciences  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4740-5423","authenticated-orcid":false,"given":"Qiong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Renji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4436-1188","authenticated-orcid":false,"given":"Daoxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Anhui Medical University  Hefei China"},{"name":"School of Life Sciences Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1268479"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-024-03220-9"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-1059"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25063142"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08617"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2010.12.014"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2018.1548935"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408\u2010021\u201000497\u20101"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2421"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aat0456"},{"issue":"10","key":"e_1_2_10_12_1","first-page":"3212","article-title":"Isocitrate Dehydrogenase 3A, a Rate\u2010limiting Enzyme of the TCA Cycle, Promotes Hepatocellular Carcinoma Migration and Invasion Through Regulation of MTA1, a Core Component of the NuRD Complex","volume":"10","author":"Liu X.","year":"2020","journal-title":"American Jounal of Cancer Research"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.02.006"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010025\u201000603\u20108"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-0575"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201035199\u20100"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018\u2010023\u201000595\u2010y"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep40921"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep41882"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2023.102672"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2009.01.002"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/ecosalplus.3.6.1.3"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201013668\u20103"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2013.13"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578\u2010017\u20100165\u20103"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13792"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.12.026"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1224892"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-024-00763-x"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010021\u201004488\u20109"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77762","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.77762","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77762","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:14:11Z","timestamp":1789132451000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.77762"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":29,"alternative-id":["10.1002\/advs.77762"],"URL":"https:\/\/doi.org\/10.1002\/advs.77762","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]},"assertion":[{"value":"2025-12-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e77762"}}