{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:55:07Z","timestamp":1790844907425,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007131","name":"Changzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["CJ20245009"],"award-info":[{"award-number":["CJ20245009"]}],"id":[{"id":"10.13039\/501100007131","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Aims<\/jats:title>\n \n We examined whether chromobox protein 5 (CBX5) contributes to temozolomide (TMZ) resistance in O\n 6<\/jats:sup>\n \u2010methylguanine\u2010DNA methyltransferase (MGMT)\u2010negative glioblastoma (GBM) and whether it is regulated by methyltransferase\u2010like 3 (METTL3)\u2010dependent N\n 6<\/jats:sup>\n \u2010methyladenosine (m\n 6<\/jats:sup>\n A) and insulin\u2010like growth factor 2 mRNA\u2010binding protein 2 (IGF2BP2).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Public datasets, clinical specimens, MGMT\u2010negative cells, and subcutaneous xenografts were examined using functional, mechanistic, and rescue assays.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In the CGGA693 cohort of the Chinese Glioma Genome Atlas, higher CBX5 expression remained associated with shorter survival after multivariable adjustment (hazard ratio 1.178, 95% confidence interval 1.050\u20131.322;\n p<\/jats:italic>\n \u2009=\u20090.005). CBX5 depletion increased TMZ sensitivity, apoptosis, and DNA damage, reduced ATM phosphorylation and RAD51 abundance, and restricted TMZ\u2010treated xenograft growth; overexpression produced reciprocal effects in\u00a0vitro. METTL3 depletion reduced CBX5 expression, mRNA stability, m\n 6<\/jats:sup>\n A enrichment, and wild\u2010type reporter activity but did not significantly affect the m\n 6<\/jats:sup>\n A motif\u2010mutant reporter. IGF2BP2 depletion reduced CBX5 protein and mRNA stability, whereas RNA immunoprecipitation supported an IGF2BP2\u2013CBX5 mRNA association. CBX5 re\u2010expression partially reversed METTL3 depletion\u2010induced effects on viability and DNA damage.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n METTL3\u2010dependent m\n 6<\/jats:sup>\n A modification and IGF2BP2\u2010associated stabilization help maintain CBX5 expression, contributing to TMZ resistance and ATM\u2013RAD51\u2010associated signaling in MGMT\u2010negative GBM models.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cns.71164","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:01:27Z","timestamp":1790841687000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["METTL3<\/scp>\n Increases Temozolomide Resistance in\n MGMT<\/scp>\n \u2010Negative Glioblastoma by Enhancing\n CBX5 mRNA<\/scp>\n Stability in an\n \n m\n 6<\/sup>\n A\n <\/scp>\n \u2010\n IGF2BP2<\/scp>\n \u2010Dependent Manner"],"prefix":"10.1002","volume":"32","author":[{"given":"Hui","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The Third Affiliated Hospital of Soochow University Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Third Affiliated Hospital of Soochow University Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daohong","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Third Affiliated Hospital of Soochow University Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cifu","family":"Qu","sequence":"additional","affiliation":[{"name":"Centre of Clinical Laboratory The First Affiliated Hospital of Soochow University Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1712-818X","authenticated-orcid":false,"given":"Jia","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Third Affiliated Hospital of Soochow University Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2024.1388700","article-title":"The Tumor\u2010Associated Fibrotic Reactions in Microenvironment Aggravate Glioma Chemoresistance","volume":"14","author":"Xu J.","year":"2024","journal-title":"Frontiers in Oncology"},{"issue":"6","key":"e_1_2_14_3_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3892\/ijo.2022.5359","article-title":"Signaling Pathways and Therapeutic Approaches in Glioblastoma Multiforme (Review)","volume":"60","author":"Khabibov 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