{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:56:38Z","timestamp":1787237798661,"version":"build-2736575974"},"reference-count":40,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81703539"],"award-info":[{"award-number":["81703539"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Brain Research"],"published-print":{"date-parts":[[2025,11]]},"DOI":"10.1016\/j.brainres.2025.149889","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T12:34:09Z","timestamp":1755693249000},"page":"149889","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"special_numbering":"C","title":["A novel derivative of rhein overcomes temozolomide resistance in glioblastoma by regulating SOX9 through m6A methylation"],"prefix":"10.1016","volume":"1866","author":[{"given":"Li","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongbiao","family":"Pi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiliang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7339-3708","authenticated-orcid":false,"given":"Jingkao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.brainres.2025.149889_b0005","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1002\/cac2.12114","article-title":"Favorable response to immunotherapy in a pancreatic neuroendocrine tumor with temozolomide-induced high tumor mutational burden","volume":"40","author":"Cao","year":"2020","journal-title":"Cancer Commun. (Lond.)."},{"key":"10.1016\/j.brainres.2025.149889_b0010","doi-asserted-by":"crossref","first-page":"17963","DOI":"10.1021\/ja3064149","article-title":"Development of cell-active N6-methyladenosine RNA demethylase FTO inhibitor","volume":"134","author":"Chen","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.brainres.2025.149889_b0015","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s10637-019-00821-4","article-title":"Discovery of a novel rhein-SAHA hybrid as a multi-targeted anti-glioblastoma drug","volume":"38","author":"Chen","year":"2020","journal-title":"Invest. New Drugs"},{"key":"10.1016\/j.brainres.2025.149889_b0020","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.1038\/s41467-018-05373-4","article-title":"A novel enhancer regulates MGMT expression and promotes temozolomide resistance in glioblastoma","volume":"9","author":"Chen","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.brainres.2025.149889_b0025","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1200\/JCO.2008.19.0694","article-title":"Phase II trial of vorinostat in recurrent glioblastoma multiforme: a north central cancer treatment group study","volume":"27","author":"Galanis","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.brainres.2025.149889_b0030","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1517\/14728222.2016.1151002","article-title":"mTOR inhibition decreases SOX2-SOX9 mediated glioma stem cell activity and temozolomide resistance","volume":"20","author":"Garros-Regulez","year":"2016","journal-title":"Expert Opin. Ther. Targets"},{"key":"10.1016\/j.brainres.2025.149889_b0035","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.cancergen.2012.10.009","article-title":"Genetics of adult glioma","volume":"205","author":"Goodenberger","year":"2012","journal-title":"Cancer Genet."},{"key":"10.1016\/j.brainres.2025.149889_b0040","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1097\/MPA.0000000000000945","article-title":"Sex determining Region Y Box 9 induces chemoresistance in pancreatic cancer cells by induction of putative cancer stem cell characteristics and its high expression predicts poor prognosis","volume":"46","author":"Higashihara","year":"2017","journal-title":"Pancreas"},{"key":"10.1016\/j.brainres.2025.149889_b0045","first-page":"3103","article-title":"In vitro study on the role of SOX9 in trastuzumab resistance of adenocarcinoma of the esophagogastric junction","volume":"15","author":"Hong","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"10.1016\/j.brainres.2025.149889_b0050","doi-asserted-by":"crossref","DOI":"10.3389\/fnut.2021.756803","article-title":"The phytochemical rhein mediates M(6)A-independent suppression of adipocyte differentiation","volume":"8","author":"Huang","year":"2021","journal-title":"Front. Nutr."},{"key":"10.1016\/j.brainres.2025.149889_b0055","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/nar\/gku1276","article-title":"Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5","volume":"43","author":"Huang","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.brainres.2025.149889_b0060","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.jconrel.2022.08.024","article-title":"Polymeric and small molecule-conjugates of temozolomide as improved therapeutic agents for glioblastoma multiforme","volume":"350","author":"Jatyan","year":"2022","journal-title":"J. Control. Release"},{"key":"10.1016\/j.brainres.2025.149889_b0065","doi-asserted-by":"crossref","first-page":"3886","DOI":"10.2174\/092986712802002446","article-title":"Strategies to improve the killing of tumors using temozolomide: targeting the DNA repair protein MGMT","volume":"19","author":"Jiang","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"10.1016\/j.brainres.2025.149889_b0070","doi-asserted-by":"crossref","first-page":"405","DOI":"10.2176\/nmc.ra.2018-0141","article-title":"Potential strategies overcoming the temozolomide resistance for glioblastoma","volume":"58","author":"Jiapaer","year":"2018","journal-title":"Neurol. Med. Chir. (Tokyo)"},{"key":"10.1016\/j.brainres.2025.149889_b0075","doi-asserted-by":"crossref","DOI":"10.1172\/JCI139542","article-title":"Inhibition of 2-hydroxyglutarate elicits metabolic reprogramming and mutant IDH1 glioma immunity in mice","volume":"131","author":"Kadiyala","year":"2021","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.brainres.2025.149889_b0080","doi-asserted-by":"crossref","first-page":"30489","DOI":"10.1038\/srep30489","article-title":"SOX9 is a novel cancer stem cell marker surrogated by osteopontin in human hepatocellular carcinoma","volume":"6","author":"Kawai","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.brainres.2025.149889_b0085","doi-asserted-by":"crossref","DOI":"10.3389\/fgene.2020.559138","article-title":"FTO - a common genetic basis for obesity and cancer","volume":"11","author":"Lan","year":"2020","journal-title":"Front. Genet."},{"key":"10.1016\/j.brainres.2025.149889_b0090","doi-asserted-by":"crossref","unstructured":"Lan, Y., Yang, T., Yue, Q., Wang, Z., Zhong, X., Luo, X., Zuo, B., Zhang, M., Zeng, T., Liu, B., Guo, H., 2023. IRP1 mediated ferroptosis reverses temozolomide resistance in glioblastoma via affecting LCN2\/FPN1 signaling axis depended on NFKB2. iScience. 26, 107377.","DOI":"10.1016\/j.isci.2023.107377"},{"key":"10.1016\/j.brainres.2025.149889_b0095","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.gendis.2016.04.007","article-title":"Temozolomide resistance in glioblastoma multiforme","volume":"3","author":"Lee","year":"2016","journal-title":"Genes Dis."},{"key":"10.1016\/j.brainres.2025.149889_b0100","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ceb.2019.07.008","article-title":"SOX9 in cartilage development and disease","volume":"61","author":"Lefebvre","year":"2019","journal-title":"Curr. Opin. Cell Biol."},{"key":"10.1016\/j.brainres.2025.149889_b0105","doi-asserted-by":"crossref","first-page":"4543","DOI":"10.1111\/cas.15072","article-title":"Long noncoding RNA just proximal to X-inactive specific transcript facilitates aerobic glycolysis and temozolomide chemoresistance by promoting stability of PDK1 mRNA in an m6A-dependent manner in glioblastoma multiforme cells","volume":"112","author":"Li","year":"2021","journal-title":"Cancer Sci."},{"key":"10.1016\/j.brainres.2025.149889_b0110","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1001\/jamaoncol.2022.5370","article-title":"Association of autologous tumor lysate-loaded dendritic cell vaccination with extension of survival among patients with newly diagnosed and recurrent glioblastoma: a phase 3 prospective externally controlled cohort trial","volume":"9","author":"Liau","year":"2023","journal-title":"JAMA Oncol."},{"key":"10.1016\/j.brainres.2025.149889_b0115","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1002\/hep.31222","article-title":"SIRT1 Regulates N(6) -Methyladenosine RNA Modification in Hepatocarcinogenesis by Inducing RANBP2-Dependent FTO SUMOylation","volume":"72","author":"Liu","year":"2020","journal-title":"Hepatology"},{"key":"10.1016\/j.brainres.2025.149889_b0120","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3389\/fbioe.2018.00089","article-title":"Link between m6A modification and cancers","volume":"6","author":"Liu","year":"2018","journal-title":"Front. Bioeng. Biotechnol."},{"key":"10.1016\/j.brainres.2025.149889_b0125","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s00401-016-1545-1","article-title":"The 2016 World Health Organization classification of tumors of the central nervous system: a summary","volume":"131","author":"Louis","year":"2016","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.brainres.2025.149889_b0130","first-page":"1864","article-title":"Interferon-\u03b2 sensitizes human malignant melanoma cells to temozolomide-induced apoptosis and autophagy","volume":"54","author":"Makita","year":"2019","journal-title":"Int. J. Oncol."},{"key":"10.1016\/j.brainres.2025.149889_b0135","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/s41467-019-14036-x","article-title":"Dual functionalized brain-targeting nanoinhibitors restrain temozolomide-resistant glioma via attenuating EGFR and MET signaling pathways","volume":"11","author":"Meng","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.brainres.2025.149889_b0140","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/bju.15019","article-title":"The N(6) -methyladenosine (m(6) a) erasers alkylation repair homologue 5 (ALKBH5) and fat mass and obesity-associated protein (FTO) are prognostic biomarkers in patients with clear cell renal carcinoma","volume":"125","author":"Strick","year":"2020","journal-title":"BJU Int."},{"key":"10.1016\/j.brainres.2025.149889_b0145","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.cell.2017.11.031","article-title":"R-2HG exhibits anti-tumor activity by targeting FTO\/m(6)A\/MYC\/CEBPA Signaling","volume":"172","author":"Su","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.brainres.2025.149889_b0150","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1002\/stem.1394","article-title":"Epigenetic regulation of SOX9 by the NF-\u03baB signaling pathway in pancreatic cancer stem cells","volume":"31","author":"Sun","year":"2013","journal-title":"Stem Cells"},{"key":"10.1016\/j.brainres.2025.149889_b0155","doi-asserted-by":"crossref","first-page":"e310","DOI":"10.1002\/ctm2.310","article-title":"FTO modifies the m6A level of MALAT and promotes bladder cancer progression","volume":"11","author":"Tao","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"10.1016\/j.brainres.2025.149889_b0160","article-title":"FTO promotes Bortezomib resistance via m6A-dependent destabilization of SOD2 expression in multiple myeloma","author":"Wang","year":"2022","journal-title":"Cancer Gene Ther."},{"key":"10.1016\/j.brainres.2025.149889_b0165","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1038\/s41417-022-00429-6","article-title":"FTO promotes Bortezomib resistance via m6A-dependent destabilization of SOD2 expression in multiple myeloma","volume":"30","author":"Wang","year":"2023","journal-title":"Cancer Gene Ther."},{"key":"10.1016\/j.brainres.2025.149889_b0170","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.semcancer.2019.09.009","article-title":"Post-translational modification of SOX family proteins: Key biochemical targets in cancer?","volume":"67","author":"Williams","year":"2020","journal-title":"Semin. Cancer Biol."},{"key":"10.1016\/j.brainres.2025.149889_b0175","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.joca.2022.01.002","article-title":"N(6)-methyladenosine RNA methyltransferase like 3 inhibits extracellular matrix synthesis of endplate chondrocytes by downregulating sex-determining region Y-Box transcription factor 9 expression under tension","volume":"30","author":"Xiao","year":"2022","journal-title":"Osteoarthritis Cartilage"},{"key":"10.1016\/j.brainres.2025.149889_b0180","first-page":"189","article-title":"Association between SOX9 and CA9 in glioma, and its effects on chemosensitivity to TMZ","volume":"53","author":"Xu","year":"2018","journal-title":"Int. J. Oncol."},{"key":"10.1016\/j.brainres.2025.149889_b0185","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/s42003-022-03420-x","article-title":"Nsun4 and Mettl3 mediated translational reprogramming of Sox9 promotes BMSC chondrogenic differentiation","volume":"5","author":"Yang","year":"2022","journal-title":"Commun. Biol."},{"key":"10.1016\/j.brainres.2025.149889_b0190","doi-asserted-by":"crossref","first-page":"2782","DOI":"10.1038\/s41467-019-10669-0","article-title":"m(6)A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade","volume":"10","author":"Yang","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.brainres.2025.149889_b0195","article-title":"Histone H3K9 lactylation confers temozolomide resistance in glioblastoma via LUC7L2-mediated MLH1 intron retention","volume":"11","author":"Yue","year":"2024","journal-title":"Adv. Sci. (weinh)"},{"key":"10.1016\/j.brainres.2025.149889_b0200","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1002\/mc.22782","article-title":"FTO regulates the chemo-radiotherapy resistance of cervical squamous cell carcinoma (CSCC) by targeting \u03b2-catenin through mRNA demethylation","volume":"57","author":"Zhou","year":"2018","journal-title":"Mol. Carcinog."}],"container-title":["Brain Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006899325004524?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006899325004524?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T04:19:05Z","timestamp":1780114745000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006899325004524"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":40,"alternative-id":["S0006899325004524"],"URL":"https:\/\/doi.org\/10.1016\/j.brainres.2025.149889","relation":{},"ISSN":["0006-8993"],"issn-type":[{"value":"0006-8993","type":"print"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A novel derivative of rhein overcomes temozolomide resistance in glioblastoma by regulating SOX9 through m6A methylation","name":"articletitle","label":"Article Title"},{"value":"Brain Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.brainres.2025.149889","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"149889"}}