{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:04:43Z","timestamp":1790255083804,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. Cuproptosis is a novel form of regulated cell death closely linked to tumor progression. Although interferon regulatory factors (IRFs) exert tumor\u2010suppressive effects in various cancers, its precise regulatory mechanisms concerning cuproptosis in HCC remain largely elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>IRF8 expression was evaluated in clinical HCC specimens and cell lines. Gain\u2010 and loss\u2010of\u2010function assays were conducted. Underlying transcriptional mechanisms were elucidated using ChIP\u2010qPCR and dual\u2010luciferase reporter assays. Subcutaneous nude mouse xenograft models were utilized to validate in\u00a0vivo phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>IRF8 was significantly downregulated in HCC. IRF8 overexpression induced oxidative stress and cuproptosis, as evidenced by excessive intracellular copper accumulation, elevated reactive oxygen species (ROS), and lipid peroxidation. Mechanistically, IRF8 directly bound to the promoter region of lipoyl synthase (LIAS) to activate its transcription. Phenotypic rescue assays confirmed that LIAS is indispensable for IRF8\u2010induced interferon (IFN\u2010\u03b1\/\u03b2) production, copper engorgement, and cuproptosis. Furthermore, in\u00a0vivo xenograft models demonstrated that IRF8 profoundly impeded tumor growth, an effect that was effectively abrogated by LIAS silencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>IRF8 inhibits HCC progression by directly upregulating LIAS to instigate lethal cuproptosis and interferon responses. The IRF8\/LIAS axis may serve as a potential mechanistic basis and candidate axis for developing HCC therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/gcc.70172","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:46:48Z","timestamp":1789012008000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>IRF8<\/scp>\n                    Suppresses Hepatocellular Carcinoma Progression Through\n                    <scp>LIAS<\/scp>\n                    \u2010Dependent\n                    <scp>IFN<\/scp>\n                    Production and Cuproptosis Activation"],"prefix":"10.1002","volume":"65","author":[{"given":"Li","family":"Zhu","sequence":"first","affiliation":[{"name":"Second Department of Hepatology Chengdu Public Health Clinical Center  Chengdu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoxia","family":"Hu","sequence":"additional","affiliation":[{"name":"Second Department of Hepatology Chengdu Public Health Clinical Center  Chengdu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Wu","sequence":"additional","affiliation":[{"name":"Second Department of Hepatology Chengdu Public Health Clinical Center  Chengdu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Duan","sequence":"additional","affiliation":[{"name":"Second Department of Hepatology Chengdu Public Health Clinical Center  Chengdu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Second Department of Hepatology Chengdu Public Health Clinical Center  Chengdu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqing","family":"Hu","sequence":"additional","affiliation":[{"name":"Second Department of Hepatology Chengdu Public Health Clinical Center  Chengdu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfan","family":"Liao","sequence":"additional","affiliation":[{"name":"Second Department of Hepatology Chengdu Public Health Clinical Center  Chengdu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Second Department of Hepatology Chengdu Public Health Clinical Center  Chengdu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Second Department of Hepatology Chengdu Public Health Clinical Center  Chengdu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[{"name":"Xiamen AMOYTOP Biotech Co, Ltd.  Xiamen People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuelian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine Chengdu Public Health Clinical Center  Chengdu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3972-5387","authenticated-orcid":false,"given":"Mei","family":"Luo","sequence":"additional","affiliation":[{"name":"Center for Precision and Translational Medicine Chengdu Public Health Clinical Center  Chengdu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12575-025-00281-6"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1526206"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.14218\/JTG.2025.00042"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21967"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1710741"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15828"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-022-00653-7"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-026-01387-x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules31030394"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.70049"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-025-09201-6"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01980-4"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s44466-025-00019-9"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11172630"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-08216-5"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32316"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0186-y"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-024-02116-x"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2025.103795"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13040764"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-024-00764-w"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14030568"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.10.002"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-025-02330-4"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3724\/abbs.2026025"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.952129"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1571788"}],"container-title":["Genes, Chromosomes and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.70172","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/gcc.70172","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.70172","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:35:16Z","timestamp":1790253316000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gcc.70172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":27,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/gcc.70172"],"URL":"https:\/\/doi.org\/10.1002\/gcc.70172","archive":["Portico"],"relation":{},"ISSN":["1045-2257","1098-2264"],"issn-type":[{"value":"1045-2257","type":"print"},{"value":"1098-2264","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-04-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70172"}}