{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:31:32Z","timestamp":1785407492955,"version":"3.56.0"},"reference-count":45,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009800","name":"Wenzhou Medical University","doi-asserted-by":"publisher","award":["89217022"],"award-info":[{"award-number":["89217022"]}],"id":[{"id":"10.13039\/100009800","id-type":"DOI","asserted-by":"publisher"}]},{"award":["89217022"],"award-info":[{"award-number":["89217022"]}],"id":[{"id":"https:\/\/ror.org\/00rd5t069","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Glioblastoma (GBM), a highly aggressive brain tumor, is characterized by poor treatment outcomes and a strong tendency to recur after therapy. Therapy-induced senescence (TIS) of GBM cells has emerged as a key driver of GBM progression and relapse. Temozolomide (TMZ), which serves as the standard chemotherapeutic agent for GBM, is known to induce senescence; however, the molecular mechanisms underlying this process remain largely unknown. In this work, we found that interferon regulatory factor-1 (IRF1) was downregulated in TMZ-induced senescent GBM cells. Functionally, knockdown of IRF1 increased the activity of senescence-associated \u03b2-galactosidase (SA-\u03b2-gal), reduced protein expression of Lamin B1, inhibited cell division, and enhanced senescence-associated secretory phenotype (SASP) of GBM cells, indicating that downregulation of IRF1 promotes senescence of GBM cells. Conversely, overexpression of IRF1 partially reversed TMZ-induced senescence. Further exploration revealed that downregulation of IRF1 reduced the expression of 2\u2032,5\u2032-oligoadenylate synthetase 2 (OAS2), and overexpression of IRF1 increased the expression of OAS2. OAS2 was also downregulated in TMZ-induced senescent GBM cells, and knockdown of OAS2 induced senescence of GBM cells as well. Taken together, our study reveals that IRF1 inhibits TMZ-induced senescence of GBM cells through OAS2, highlighting a novel regulatory axis that may offer potential therapeutic targets for improving GBM treatment.<\/jats:p>","DOI":"10.3390\/cells15131149","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T01:03:56Z","timestamp":1782349436000},"page":"1149","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["IRF1 Inhibits Therapy-Induced Senescence of Glioblastoma Cells Through OAS2"],"prefix":"10.3390","volume":"15","author":[{"given":"Genli","family":"Ma","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangcong","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Shen","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanli","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4912-770X","authenticated-orcid":false,"given":"Xingxing","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"v1","DOI":"10.1093\/neuonc\/noz150","article-title":"CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012\u20132016","volume":"21","author":"Ostrom","year":"2019","journal-title":"Neuro-Oncology"},{"key":"ref_2","first-page":"363","article-title":"Cancer treatment and survivorship statistics, 2019","volume":"69","author":"Miller","year":"2019","journal-title":"CA Cancer J. 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