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dc.contributor.authorMensah, AAen_US
dc.contributor.authorCascione, Len_US
dc.contributor.authorGaudio, Een_US
dc.contributor.authorTarantelli, Cen_US
dc.contributor.authorBomben, Ren_US
dc.contributor.authorBernasconi, Een_US
dc.contributor.authorZito, Den_US
dc.contributor.authorLampis, Aen_US
dc.contributor.authorHahne, JCen_US
dc.contributor.authorRinaldi, Aen_US
dc.contributor.authorStathis, Aen_US
dc.contributor.authorZucca, Een_US
dc.contributor.authorKwee, Ien_US
dc.contributor.authorGattei, Ven_US
dc.contributor.authorValeri, Nen_US
dc.contributor.authorRiveiro, MEen_US
dc.contributor.authorBertoni, Fen_US
dc.coverage.spatialItalyen_US
dc.date.accessioned2018-11-14T11:26:34Z
dc.date.issued2018-08-03en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30076183en_US
dc.identifierhaematol.2018.191684en_US
dc.identifier.citationHaematologica, 2018en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2934
dc.identifier.eissn1592-8721en_US
dc.identifier.doi10.3324/haematol.2018.191684en_US
dc.description.abstractAberrant changes in microRNA expression contribute to lymphomagenesis. Bromodomain and extra-terminal domain inhibitors like OTX015 (MK-8628, birabresib) have demonstrated preclinical and clinical activity in haematological tumours. MicroRNA profiling of diffuse large B-cell lymphoma cells treated with OTX015 revealed changes in the expression levels of a limited number of microRNAs, including miR-92a-1-5p, miR-21-3p, miR-155-5p and miR-96-5p. Analysis of publicly available ChIP-Seq data of diffuse large B-cell lymphoma cells treated with bromodomain and extra-terminal domain (BET) inhibitors showed that the BET family member BRD4 bound to the upstream regulatory regions of multiple microRNA genes and that this binding decreased following BET inhibition. Alignment of our microRNA profiling data with the BRD4 ChIP-Seq data revealed that microRNAs downregulated by OTX015 also exhibited reduced BRD4 binding in their promoter regions following treatment with another bromodomain and extra-terminal domain inhibitor, JQ1, indicating that BRD4 directly contributes to microRNA expression in lymphoma. Treatment with bromodomain and extra-terminal domain inhibitors also decreased the expression of the arginine methyltransferase PRMT5, which plays a crucial role in B-cell transformation and negatively modulates the transcription of miR-96-5p. The data presented here indicate that in addition to the previously observed effects on the expression of coding genes, bromodomain and extra-terminal domain inhibitors also modulate the expression of microRNAs involved in lymphomagenesis.en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserveden_US
dc.subjectAggressive Non-Hodgkin's Lymphomaen_US
dc.subjectEpigeneticsen_US
dc.subjectMolecular Pharmacologyen_US
dc.subjectmiRNAen_US
dc.titleBromodomain and extra-terminal domain inhibition modulates the expression of pathologically relevant microRNAs in diffuse large B-cell lymphoma.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-07-31en_US
rioxxterms.versionofrecord10.3324/haematol.2018.191684en_US
rioxxterms.licenseref.startdate2018-08-03en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfHaematologicaen_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gastrointestinal Cancer Biology and Genomics
pubs.publication-statusPublished onlineen_US
pubs.embargo.termsNot knownen_US
icr.researchteamGastrointestinal Cancer Biology and Genomicsen_US
dc.contributor.icrauthorValeri, Nicolaen_US
dc.contributor.icrauthorHahne, Jensen_US
dc.contributor.icrauthorLampis, Andreaen_US


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