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Identification of novel non-coding RNA-based negative feedback regulating the expression of the oncogenic transcription factor GLI1

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dc.creatorVillegas Gálvez, Victoria Eugenia
dc.creatorRahman, Mohammed Ferdous-Ur
dc.creatorFernandez-Barrena, Maite G.
dc.creatorDiao, Yumei
dc.creatorLiapi, Eleni
dc.creatorSonkoly, Eniko
dc.creatorStahle, Mona
dc.creatorPivarcsi, Andor
dc.creatorAnnaratone, Laura
dc.creatorSapino, Anna
dc.creatorRamírez Clavijo, Sandra Rocío
dc.creatorBurglin, Thomas R.
dc.creatorShimokawa, Takashi
dc.creatorRamachandran, Saraswathi
dc.creatorKapranov, Philipp
dc.creatorFernandez-Zapico, Martin E.
dc.creatorZaphiropoulos, Peter G.
dc.creator.googleVillegas, Victoria E.spa
dc.creator.googleRahman, Mohammed Ferdous-Urspa
dc.creator.googleFernandez-Barrena, Maite G.spa
dc.creator.googleDiao, Yumeispa
dc.creator.googleLiapi, Elenispa
dc.creator.googleSonkoly, Enikospa
dc.creator.googleSonkoly, Enikospa
dc.creator.googleRamırez Clavijo, Sandraspa
dc.creator.googleShimokawa, Takashispa
dc.creator.googleRamachandran, Saraswathispa
dc.creator.googleKapranov, Philippspa
dc.creator.googleFernandez-Zapico, Martin E.spa
dc.creator.googleZaphiropoulos, Peter G.spa
dc.date.accessioned2018-11-21T16:32:41Z
dc.date.available2018-11-21T16:32:41Z
dc.date.created2014
dc.date.issued2014
dc.description.abstractNon-coding RNAs are a complex class of nucleic acids, with growing evidence supporting regulatory roles in gene expression. Here we identify a non-coding RNA located head-to-head with the gene encoding the Glioma-associated oncogene 1 (GLI1), a transcriptional effector of multiple cancer-associated signaling pathways. The expression of this three-exon GLI1 antisense (GLI1AS) RNA in cancer cells was concordant with GLI1 levels. siRNAs knockdown of GLI1AS up-regulated GLI1 and increased cellular proliferation and tumor growth in a xenograft model system. Conversely, GLI1AS overexpression decreased the levels of GLI1, its target genes PTCH1 and PTCH2, and cellular proliferation. Additionally, we demonstrate that GLI1 knockdown reduced GLI1AS, while GLI1 overexpression increased GLI1AS, supporting the role of GLI1AS as a target gene of the GLI1 transcription factor. Activation of TGFβ and Hedgehog signaling, two known regulators of GLI1 expression, conferred a concordant up-regulation of GLI1 and GLI1AS in cancer cells. Finally, analysis of the mechanism underlying the interplay between GLI1 and GLI1AS indicates that the non-coding RNA elicits a local alteration of chromatin structure by increasing the silencing mark H3K27me3 and decreasing the recruitment of RNA polymerase II to this locus. Taken together, the data demonstrate the existence of a novel non-coding RNA-based negative feedback loop controlling GLI1 levels, thus expanding the repertoire of mechanisms regulating the expression of this oncogenic transcription factor © 2014 Federation of European Biochemical Societies.eng
dc.format.mimetypeapplication/pdf
dc.identifier.issnISSN 1574-7891
dc.identifier.urihttp://repository.urosario.edu.co/handle/10336/18719
dc.language.isoengspa
dc.relation.citationEndPage926
dc.relation.citationIssueNo. 5
dc.relation.citationStartPage912
dc.relation.citationTitleMolecular Oncology
dc.relation.citationVolumeVol. 8
dc.relation.ispartofMolecular Oncology, ISSN: 1574-7891, Vol. 8/No. 5 (2014) pp. 912-926spa
dc.relation.urihttps://febs.onlinelibrary.wiley.com/doi/epdf/10.1016/j.molonc.2014.03.009spa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.rights.cchttps://creativecommons.org/licenses/by-nc-nd/4.0/spa
dc.source.bibliographicCitationBerretta, J., Pinskaya, M., Morillon, A., A cryptic unstable transcript mediates transcriptional trans-silencing of the Ty1 retrotransposon in S. cerevisiae (2008) Genes Dev., 22, pp. 615-626spa
dc.source.instnameinstname:Universidad del Rosario
dc.source.reponamereponame:Repositorio Institucional EdocUR
dc.subjectCancerspa
dc.subjectChromatinspa
dc.subjectGene Expressionspa
dc.subjectGli1spa
dc.subjectNon-Coding Rnaspa
dc.subjectTranscriptionspa
dc.subject.decsComplementary Rnaspa
dc.subject.decsProtein Patched 1spa
dc.subject.decsProtein Patched 2spa
dc.subject.decsRna Polymerase Iispa
dc.subject.decsSmall Interfering Rnaspa
dc.subject.decsSonic Hedgehog Proteinspa
dc.subject.decsTranscription Factor Gli1spa
dc.subject.decsUntranslated Rnaspa
dc.subject.decsChromatinspa
dc.subject.decsGli Proteinspa
dc.subject.decsOncoproteinspa
dc.subject.decsRna Polymerase Iispa
dc.subject.decsSonic Hedgehog Proteinspa
dc.subject.decsTransactivator Proteinspa
dc.subject.decsTransforming Growth Factor Betaspa
dc.subject.decsUntranslated Rnaspa
dc.subject.decsTransforming Growth Factor Betaspa
dc.subject.decsArticlespa
dc.subject.decsBreast Cancerspa
dc.subject.decsBreast Fibroadenomaspa
dc.subject.decsCancer Cellspa
dc.subject.decsCell Proliferationspa
dc.subject.decsChromatin Assembly And Disassemblyspa
dc.subject.decsChromatin Immunoprecipitationspa
dc.subject.decsChromatin Structurespa
dc.subject.decsChromosome 21Qspa
dc.subject.decsComparative Studyspa
dc.subject.decsControlled Studyspa
dc.subject.decsDown Regulationspa
dc.subject.decsExonspa
dc.subject.decsGene Expressionspa
dc.subject.decsGene Silencingspa
dc.subject.decsGenetic Transfectionspa
dc.subject.decsHumanspa
dc.subject.decsHuman Tissuespa
dc.subject.decsNegative Feedbackspa
dc.subject.decsNucleotide Sequencespa
dc.subject.decsOncogenespa
dc.subject.decsPolyadenylationspa
dc.subject.decsPriority Journalspa
dc.subject.decsPromoter Regionspa
dc.subject.decsRegulatory Mechanismspa
dc.subject.decsRna Sequencespa
dc.subject.decsSignal Transductionspa
dc.subject.decsTranscription Initiation Sitespa
dc.subject.decsTumor Growthspa
dc.subject.decsUpregulationspa
dc.subject.decsChromatinspa
dc.subject.decsGene Expression Regulationspa
dc.subject.decsGeneticsspa
dc.subject.decsMetabolismspa
dc.subject.decsNeoplasmspa
dc.subject.decsPathologyspa
dc.subject.decsTranscription Initiationspa
dc.subject.decsTumor Cell Linespa
dc.subject.decsArticlespa
dc.subject.decsGenetic Transcriptionspa
dc.subject.decsHuman Cellspa
dc.subject.decsErinaceidaespa
dc.subject.decsCell Line, Tumorspa
dc.subject.decsChromatinspa
dc.subject.decsGene Expression Regulation, Neoplasticspa
dc.subject.decsHedgehog Proteinsspa
dc.subject.decsHumansspa
dc.subject.decsNeoplasmsspa
dc.subject.decsOncogene Proteinsspa
dc.subject.decsRna Polymerase Iispa
dc.subject.decsRna, Untranslatedspa
dc.subject.decsSignal Transductionspa
dc.subject.decsTrans-Activatorsspa
dc.subject.decsTranscriptional Activationspa
dc.subject.decsTransforming Growth Factor Betaspa
dc.subject.lembCromatinaspa
dc.subject.lembExpresión genéticaspa
dc.subject.lembCáncerspa
dc.titleIdentification of novel non-coding RNA-based negative feedback regulating the expression of the oncogenic transcription factor GLI1spa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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