Show simple item record

dc.contributor.authorMensah, AA
dc.contributor.authorCascione, L
dc.contributor.authorGaudio, E
dc.contributor.authorTarantelli, C
dc.contributor.authorBomben, R
dc.contributor.authorBernasconi, E
dc.contributor.authorZito, D
dc.contributor.authorLampis, A
dc.contributor.authorHahne, JC
dc.contributor.authorRinaldi, A
dc.contributor.authorStathis, A
dc.contributor.authorZucca, E
dc.contributor.authorKwee, I
dc.contributor.authorGattei, V
dc.contributor.authorValeri, N
dc.contributor.authorRiveiro, ME
dc.contributor.authorBertoni, F
dc.date.accessioned2018-11-14T11:26:34Z
dc.date.issued2018-12
dc.identifier.citationHaematologica, 2018, 103 (12), pp. 2049 - 2058
dc.identifier.issn0390-6078
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2934
dc.identifier.eissn1592-8721
dc.identifier.doi10.3324/haematol.2018.191684
dc.description.abstractAberrant changes in microRNA expression contribute to lymphomagenesis. Bromodomain and extra-terminal domain inhibitors such as OTX015 (MK-8628, birabresib) have demonstrated preclinical and clinical activity in hematologic tumors. 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 chromatin immunoprecipitation sequencing 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 chromatin immunoprecipitation sequencing 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 contributes directly 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 previously observed effects on the expression of coding genes, bromodomain and extra-terminal domain inhibitors also modulate the expression of microRNAs involved in lymphomagenesis.
dc.formatPrint-Electronic
dc.format.extent2049 - 2058
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectCell Line, Tumor
dc.subjectHumans
dc.subjectAcetanilides
dc.subjectHeterocyclic Compounds, 3-Ring
dc.subjectCell Cycle Proteins
dc.subjectNuclear Proteins
dc.subjectTranscription Factors
dc.subjectMicroRNAs
dc.subjectGene Expression Profiling
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectProtein Binding
dc.subjectLymphoma, Large B-Cell, Diffuse
dc.subjectProtein Domains
dc.titleBromodomain and extra-terminal domain inhibition modulates the expression of pathologically relevant microRNAs in diffuse large B-cell lymphoma.
dc.typeJournal Article
dcterms.dateAccepted2018-07-31
rioxxterms.versionofrecord10.3324/haematol.2018.191684
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc/4.0
rioxxterms.licenseref.startdate2018-12
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfHaematologica
pubs.issue12
pubs.notesNot known
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/Evolutionary Genomics & Modelling
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gastrointestinal Cancer Biology and Genomics
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/Evolutionary Genomics & Modelling
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gastrointestinal Cancer Biology and Genomics
pubs.publication-statusPublished
pubs.volume103
pubs.embargo.termsNot known
icr.researchteamEvolutionary Genomics & Modellingen_US
icr.researchteamGastrointestinal Cancer Biology and Genomicsen_US
dc.contributor.icrauthorHahne, Jensen
dc.contributor.icrauthorLampis, Andreaen
dc.contributor.icrauthorValeri, Nicolaen


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record