{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:21:41Z","timestamp":1787728901061,"version":"build-2784847793"},"reference-count":47,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"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":["82600022"],"award-info":[{"award-number":["82600022"]}],"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":["82403695"],"award-info":[{"award-number":["82403695"]}],"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":["82273053"],"award-info":[{"award-number":["82273053"]}],"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":["824B2086"],"award-info":[{"award-number":["824B2086"]}],"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":["82473271"],"award-info":[{"award-number":["82473271"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020084","name":"Guangzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["2025B03J0019"],"award-info":[{"award-number":["2025B03J0019"]}],"id":[{"id":"10.13039\/501100020084","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023M744036"],"award-info":[{"award-number":["2023M744036"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002402","name":"Sun Yat-sen University","doi-asserted-by":"publisher","award":["2017004"],"award-info":[{"award-number":["2017004"]}],"id":[{"id":"10.13039\/501100002402","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Resistance to immune checkpoint blockade substantially limits its clinical efficacy in head and neck squamous cell carcinoma(HNSCC). ZC3H13 is a component of the N6\u2010methyladenosine writer complex, but its roles in HNSCC progression and response to anti\u2010programmed cell death protein 1(anti\u2010PD\u20101) therapy remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The expression and clinical relevance of ZC3H13 were evaluated using clinical cohorts and publicly available transcriptomic datasets. Gain\u2010 and loss\u2010of\u2010function experiments were performed to determine the effects of ZC3H13 on the malignant phenotypes of HNSCC cells. An epithelial\u2010specific ZC3H13 conditional knockout mouse model of 4\u2010nitroquinoline\u20101\u2010oxide\u2010induced oral tumorigenesis was used to assess tumor development and responsiveness to anti\u2010PD\u20101 therapy. N6\u2010methyladenosine modification, RNA stability and functional rescue assays were conducted to investigate the underlying molecular mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ZC3H13 was upregulated in HNSCC and was associated with poor prognosis and a limited response to anti\u2010PD\u20101 treatment. ZC3H13 promoted the proliferation and invasion of HNSCC cells, whereas epithelial\u2010specific ablation of ZC3H13 suppressed oral tumorigenesis and enhanced the therapeutic efficacy of anti\u2010PD\u20101 treatment. Mechanistically, ZC3H13 regulated the N6\u2010methyladenosine modification of cyclin D1(CCND1) mRNA and promoted its IGF2BP1\u2010dependent stabilization, thereby contributing to malignant tumor phenotypes and alterations in immunosuppressvie features.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The ZC3H13\/IGF2BP1\/CCND1 regulatory axis contributes to HNSCC progression and resistance to anti\u2010PD\u20101 therapy. These findings identify ZC3H13 as a potential therapeutic target for improving the efficacy of anti\u2010PD\u20101 treatment in HNSCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70750","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T08:14:56Z","timestamp":1785140096000},"source":"Crossref","is-referenced-by-count":0,"title":["ZC3H13\u2010mediated m6A stabilization of CCND1 promotes malignant progression and is associated with poor anti\u2010PD\u20101 response in HNSCC"],"prefix":"10.1002","volume":"16","author":[{"given":"Wenqing","family":"Chen","sequence":"first","affiliation":[{"name":"Otorhinolaryngology Hospital The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Li","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology Hospital The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Center for Translational Medicine The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7457-2816","authenticated-orcid":false,"given":"Caihua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Center for Translational Medicine The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology Hospital The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Sun","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology Hospital The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingyi","family":"Li","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlong","family":"Yang","sequence":"additional","affiliation":[{"name":"Clinical Research Center Affiliated Hospital of Guangdong Medical University  Zhanjiang Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Lei","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology Hospital The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Li","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology Hospital The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"},{"name":"Department of Laboratory Medicine and Center for Translational Medicine The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201023\u20103594"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010020\u201000224\u20103"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27619-4"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2025.102938"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.03.017"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010023\u201001835\u20102"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.06.009"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100411"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201021\u20103570"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010024\u201001998\u2010y"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010023\u201000774\u2010x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420\u2010024\u201002092\u20102"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u201003135\u20101"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422\u2010022\u201000725\u20108"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010025\u201007889\u20102"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1612041"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41389\u2010023\u201000502\u20101"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201024\u20102562"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427\u2010021\u20102140\u20108"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201024\u20101378"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010018\u20100045\u2010z"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010024\u201001994\u20100"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022016597"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010biochem\u2010052521\u2010035949"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010immunol\u2010101921\u2010045401"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(19)32591\u20107"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201020\u20100197"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201037379\u2010y"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.02.015"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201023892\u20105"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.715"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201024\u20103975"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27551"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201023\u20100225"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI178540"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010biochem\u2010052521\u2010035330"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.01.006"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010020\u201000450\u2010x"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388\u2010023\u201002865\u20106"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010023\u201005763\u20107"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01620"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20220729"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature23465"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2023.188912"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2035"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"}],"container-title":["Clinical and Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ctm2.70750","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ctm2.70750","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ctm2.70750","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:39:54Z","timestamp":1787726394000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ctm2.70750"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":47,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/ctm2.70750"],"URL":"https:\/\/doi.org\/10.1002\/ctm2.70750","archive":["Portico"],"relation":{},"ISSN":["2001-1326","2001-1326"],"issn-type":[{"value":"2001-1326","type":"print"},{"value":"2001-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]},"article-number":"e70750"}}