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dc.contributor.authorKloetgen, Andreas
dc.contributor.authorDuggimpudi, Sujitha
dc.contributor.authorSchuschel, Konstantin
dc.contributor.authorHezaveh, Kebria
dc.contributor.authorPicard, Daniel
dc.contributor.authorSchaal, Heiner
dc.contributor.authorRemke, Marc
dc.contributor.authorKlusmann, Jan-Henning
dc.contributor.authorBorkhardt, Arndt
dc.contributor.authorMcHardy, Alice C
dc.contributor.authorHoell, Jessica I
dc.date.accessioned2020-08-05T14:27:31Z
dc.date.available2020-08-05T14:27:31Z
dc.date.issued2020-06-23
dc.identifier.citationInt J Mol Sci. 2020;21(12):4453. Published 2020 Jun 23. doi:10.3390/ijms21124453.en_US
dc.identifier.pmid32585856
dc.identifier.doi10.3390/ijms21124453
dc.identifier.urihttp://hdl.handle.net/10033/622389
dc.description.abstractMedulloblastomas arise from undifferentiated precursor cells in the cerebellum and account for about 20% of all solid brain tumors during childhood; standard therapies include radiation and chemotherapy, which oftentimes come with severe impairment of the cognitive development of the young patients. Here, we show that the posttranscriptional regulator Y-box binding protein 1 (YBX1), a DNA- and RNA-binding protein, acts as an oncogene in medulloblastomas by regulating cellular survival and apoptosis. We observed different cellular responses upon YBX1 knockdown in several medulloblastoma cell lines, with significantly altered transcription and subsequent apoptosis rates. Mechanistically, PAR-CLIP for YBX1 and integration with RNA-Seq data uncovered direct posttranscriptional control of the heterochromatin-associated gene CBX5; upon YBX1 knockdown and subsequent CBX5 mRNA instability, heterochromatin-regulated genes involved in inflammatory response, apoptosis and death receptor signaling were de-repressed. Thus, YBX1 acts as an oncogene in medulloblastoma through indirect transcriptional regulation of inflammatory genes regulating apoptosis and represents a promising novel therapeutic target in this tumor entity.en_US
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectPAR-CLIPen_US
dc.subjectRNA-Seqen_US
dc.subjectY-box binding protein 1en_US
dc.subjectmedulloblastomaen_US
dc.subjectpost-transcriptional gene regulationen_US
dc.titleYBX1 Indirectly Targets Heterochromatin-Repressed Inflammatory Response-Related Apoptosis Genes through Regulating CBX5 mRNA.en_US
dc.typeArticleen_US
dc.identifier.eissn1422-0067
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalInternational journal of molecular sciencesen_US
dc.source.volume21
dc.source.issue12
refterms.dateFOA2020-08-05T14:27:32Z
dc.source.journaltitleInternational journal of molecular sciences
dc.source.countryInternational
dc.source.countrySwitzerland


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