{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:36:55Z","timestamp":1787665015447,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T00:00:00Z","timestamp":1748044800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100022963","name":"Key Research and Development Program of Zhejiang Province","doi-asserted-by":"publisher","award":["2021C03120"],"award-info":[{"award-number":["2021C03120"]}],"id":[{"id":"10.13039\/100022963","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070151"],"award-info":[{"award-number":["32070151"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>As an essential transcription factor, Myc\u2010associated zinc\u2010finger protein (MAZ) is frequently upregulated in many human tumors and is a well\u2010documented oncogene.\u2009However, we found high expression of MAZ was closely associated with good survival outcomes in patients with stomach adenocarcinoma (STAD), and the underlying mechanism involved remains to be elucidated. We hypothesize that alternative splicing of MAZ plays an important role.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pan\u2010cancer analysis of MAZ expression and prognostic significance was performed using The Cancer Genome Atlas (TCGA) data, with emphasis on its divergent prognostic impact in gastric cancer (GC). MAZ protein levels were further validated in 356 GC tissue samples via immunohistochemistry. Functional investigations encompassed MAZ knockout (KO) and isoform\u2010specific rescue experiments to assess GC cell migration, alongside quantification of MAZ alternative splicing rates (PSI). Additionally, RNA immunoprecipitation sequencing (RIP\u2010seq) identified PUF60\u2010mediated regulation of MAZ isoforms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MAZ was upregulated in GC but served as an independent protective prognostic factor. MAZ\u2010KO enhanced GC cell migration, while isoform\u2010specific re\u2010expression revealed divergent roles: MAZ\u20102 promoted migration, whereas MAZ\u20101 and MAZ\u20103 suppressed it. Notably, MAZ\u20102 is highly expressed in GC and is associated with poor survival prognosis of patients. Lower PSI values of MAZ\u20102 were detected in GC. MAZ transcripts were directly bound by PUF60. PUF60 knockdown caused MAZ splice isoform switch, thereby enhancing GC cell migration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The prognostic difference of MAZ in GC stems from isoform\u2010specific functional antagonism, with cell migration phenotypes governed by the MAZ\u20101\/3 versus MAZ\u20102 ratio. Targeting MAZ alternative splicing, particularly via PUF60 modulation, represents a novel therapeutic strategy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70977","type":"journal-article","created":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T08:03:46Z","timestamp":1748073826000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>PUF60<\/scp>\u2010Regulated Isoform Switching of <scp>MAZ<\/scp> Modulates Gastric Cancer Cell Migration"],"prefix":"10.1002","volume":"14","author":[{"given":"Dong","family":"Xing","sequence":"first","affiliation":[{"name":"Wenzhou Collaborative Innovation Center of Gastrointestinal Cancer in Basic Research and Precision Medicine, Wenzhou Key Laboratory of Cancer\u2010Related Pathogens and Immunity, Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, School of Basic Medical Sciences Wenzhou Medical University  Wenzhou 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