{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:35:32Z","timestamp":1793122532888,"version":"4.5.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32270746"],"award-info":[{"award-number":["32270746"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82203247"],"award-info":[{"award-number":["82203247"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82203415"],"award-info":[{"award-number":["82203415"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LZ23C060002"],"award-info":[{"award-number":["LZ23C060002"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LZ24H160004"],"award-info":[{"award-number":["LZ24H160004"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["226-2025-00101"],"award-info":[{"award-number":["226-2025-00101"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["K20220228"],"award-info":[{"award-number":["K20220228"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>CEBPB is a critical driver of mesenchymal transformation and aggressiveness in glioblastoma (GBM). However, fundamental questions remain regarding its dynamic regulation within the GBM microenvironment and its precise mechanistic role in orchestrating epigenetic and transcriptional reprogramming.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To decode the CEBPB cistrome and its role in chromatin remodeling in GBM, we performed an integrated analysis of CEBPB\/H3K27ac ChIP-seq, CEBPB HiChIP, and RNA-seq. Transcriptional and translational control of CEBPB expression was delineated through enhancer profiling, bioinformatics analysis, siRNA screening, synthetic reporter assays, and immunoblotting. Functional investigations were conducted using patient-derived tumor spheroids, human and murine glioma cell lines, and xenograft\/allograft murine models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We demonstrate that CEBPB is a super-enhancer-driven gene, with all 3 isoforms (LAP1, LAP2, LIP) overexpressed in primary GBM. Functional analyses reveal that LAP1 and LAP2 are essential for tumorigenesis, while LIP specifically promotes in vivo growth in a LAP1\/LAP2-dependent manner. We further reveal that myeloid-derived oncostatin M (OSM) potently induces CEBPB expression through OSMR-STAT3-mediated transcription and a novel eIF4G2-dependent alternative translation process. Mechanistically, eIF4G2 directs selective LIP synthesis by engaging a specialized 3\u2032 UTR translation enhancer within the CEBPB transcript. Genetic ablation of EIF4G2 suppresses tumorigenicity, a phenotype fully rescued by LIP overexpression. Ultimately, CEBPB isoforms coordinately rewire the epigenetic landscape, remodeling super-enhancers and chromatin looping to establish an oncogenic transcriptional program that activates key effectors like CHI3L1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This work elucidates a pathogenic axis in glioblastoma wherein OSM signaling and eIF4G2-mediated alternative translation converge on CEBPB isoforms to enforce enhancer architectures and chromatin interactions for oncogenic transcription.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noag246","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:56:35Z","timestamp":1791374195000},"source":"Crossref","is-referenced-by-count":0,"title":["CEBPB integrates OSM signaling and eIF4G2-mediated alternative translation to configure enhancer landscape and sustain oncogenic CHI3L1 in glioblastoma"],"prefix":"10.1093","author":[{"given":"Jiyang","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Biochemistry, College of Life Sciences, Zhejiang University , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9644-7062","authenticated-orcid":false,"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, College of Life Sciences, Zhejiang University , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Department of Radiology, Chongqing University Three Gorges Hospital, Chongqing University , Chongqing,","place":["China"]},{"name":"National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Xiangya Hospital , Changsha,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Xie","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, College of Life Sciences, Zhejiang University , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9286-1344","authenticated-orcid":false,"given":"Xingze","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, College of Life Sciences, Zhejiang University , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipeng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, College of Life Sciences, Zhejiang University , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Pediatric Cancer Research Center, Children\u2019s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents\u2019 Health and Diseases , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital, Central South University , Changsha,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suya","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Pediatric Cancer Research Center, Children\u2019s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents\u2019 Health and Diseases , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1640-6868","authenticated-orcid":false,"given":"Yongjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9402-6487","authenticated-orcid":false,"given":"Hangzhe","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5370-8334","authenticated-orcid":false,"given":"Yue","family":"Yu","sequence":"additional","affiliation":[{"name":"Neuroscience Care Unit, The Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeming","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Xiangya Hospital, Central South University , Changsha,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6624-1593","authenticated-orcid":false,"given":"Tuan Zea","family":"Tan","sequence":"additional","affiliation":[{"name":"Cancer Science Institute of Singapore, National University of Singapore , Singapore,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold Phillip","family":"Koeffler","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Cedars-Sinai Medical Center , Los Angeles, 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