{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T10:15:39Z","timestamp":1771236939735,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"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":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Gliomas are characterized by high incidence, high recurrence rate, high malignancy, high aggressiveness, high therapeutic difficulty, poor clinical prognosis, and high mortality. Therefore, overcoming temozolomide (TMZ) resistance in glioma has become a research hotspot. This study will investigate the effects of glioma cell\u2010derived apoptotic extracellular vesicles (apoEVs) on tumorigenesis and TMZ resistance in glioma. apoEVs derived from TMZ\u2010induced apoptotic glioma cells were isolated, extracted, and characterized. The effects of apoEVs and the extracellular vesicle inhibitor GW4869 on the TMZ resistance, migratory, and invasive capacities of glioma cells were explored using CCK\u20108, plate cloning assays, flow cytometry, and Transwell assays. Ago2 and luciferase assays were used to confirm the lncRNA\u2010XIST\/miR\u201029c\/SP1 axis. A subcutaneous tumor xenograft model was established in nude mice using LN229 cells to validate the in vivo function and related mechanisms of apoEVs. Apoptotic glioma cell\u2010derived apoEVs had consistent exosomal characteristics. ApoEVs promoted glioma cell TMZ resistance and migratory and invasive capacities in vitro and in vivo, effects that were effectively reversed by GW4869. Mechanistically, glioma cell\u2010derived apoEVs promoted glioma cell epithelial\u2010mesenchymal transition (EMT) by delivering lncRNA\u2010XIST, which regulated the miR\u201029c\/SP1\/MGMT axis. This study revealed a novel mechanism by which lncRNA\u2010XIST promoted the malignant phenotype of glioma cells, which was found to be encapsulated inside apoptotic glioma cells rather than being released directly to the extracellular compartment. This finding revealed that it was possible to intervene in the function of lncRNA\u2010XIST by inhibiting apoEV formation, thereby providing a new therapeutic avenue targeting lncRNA\u2010XIST to modulate TMZ resistance in glioma.<\/jats:p>","DOI":"10.1002\/jbt.70735","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T09:24:55Z","timestamp":1771233895000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glioma Cell\u2010Derived Apoptotic Extracellular Vesicles Promote Tumorigenesis and Temozolomide Resistance by Delivering LncRNA\u2010XIST"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1856-2290","authenticated-orcid":false,"given":"Peng","family":"Du","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital Xinjiang Medical University Urumqi Xinjiang Uygur Autonomous Region China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0813-4073","authenticated-orcid":false,"given":"Yangtai","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renji Hospital Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"issue":"1","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12943-022-01513-z","article-title":"Glioma Targeted Therapy: Insight Into Future of Molecular Approaches","volume":"21","author":"Yang K.","year":"2022","journal-title":"Molecular Cancer"},{"issue":"3","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1002\/art.41988","article-title":"SH2 Domain\u2010Containing Phosphatase 2 Inhibition Attenuates Osteoarthritis by Maintaining Homeostasis of Cartilage Metabolism via the Docking Protein 1\/Uridine Phosphorylase 1\/Uridine Cascade","volume":"74","author":"Liu Q.","year":"2022","journal-title":"Arthritis and Rheumatology"},{"issue":"8","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1038\/s41417-023-00627-w","article-title":"Extracellular Vesicles Released by Glioma Cells Are Decorated by Annexin A2 Allowing for Cellular Uptake via Heparan Sulfate","volume":"30","author":"Song Y.","year":"2023","journal-title":"Cancer Gene Therapy"},{"issue":"9","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"2734","DOI":"10.7150\/thno.82005","article-title":"Current Advances in Temozolomide Encapsulation for the Enhancement of Glioblastoma Treatment","volume":"13","author":"Iturrioz\u2010Rodr\u00edguez N.","year":"2023","journal-title":"Theranostics"},{"issue":"2","key":"e_1_2_11_6_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbcan.2021.188616","article-title":"Elucidating the Mechanisms of Temozolomide Resistance in Gliomas and the Strategies to Overcome the Resistance","volume":"1876","author":"Tomar M. 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