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dc.contributor.authorXavier-Magalhães, A
dc.contributor.authorGonçalves, CS
dc.contributor.authorFogli, A
dc.contributor.authorLourenço, T
dc.contributor.authorPojo, M
dc.contributor.authorPereira, B
dc.contributor.authorRocha, M
dc.contributor.authorLopes, MC
dc.contributor.authorCrespo, I
dc.contributor.authorRebelo, O
dc.contributor.authorTão, H
dc.contributor.authorLima, J
dc.contributor.authorMoreira, R
dc.contributor.authorPinto, AA
dc.contributor.authorJones, C
dc.contributor.authorReis, RM
dc.contributor.authorCostello, JF
dc.contributor.authorArnaud, P
dc.contributor.authorSousa, N
dc.contributor.authorCosta, BM
dc.date.accessioned2021-01-21T14:41:18Z
dc.date.issued2018-03
dc.identifier.citationOncotarget, 2018, 9 (21), pp. 15740 - 15756
dc.identifier.issn1949-2553
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4299
dc.identifier.eissn1949-2553
dc.identifier.doi10.18632/oncotarget.24597
dc.description.abstractThe lncRNA HOTAIR has been implicated in several human cancers. Here, we evaluated the molecular alterations and upstream regulatory mechanisms of HOTAIR in glioma, the most common primary brain tumors, and its clinical relevance. HOTAIR gene expression, methylation, copy-number and prognostic value were investigated in human gliomas integrating data from online datasets and our cohorts. High levels of HOTAIR were associated with higher grades of glioma, particularly IDH wild-type cases. Mechanistically, HOTAIR was overexpressed in a gene dosage-independent manner, while DNA methylation levels of particular CpGs in HOTAIR locus were associated with HOTAIR expression levels in GBM clinical specimens and cell lines. Concordantly, the demethylating agent 5-Aza-2'-deoxycytidine affected HOTAIR transcriptional levels in a cell line-dependent manner. Importantly, HOTAIR was frequently co-expressed with HOXA9 in high-grade gliomas from TCGA, Oncomine, and our Portuguese and French datasets. Integrated in silico analyses, chromatin immunoprecipitation, and qPCR data showed that HOXA9 binds directly to the promoter of HOTAIR . Clinically, GBM patients with high HOTAIR expression had a significantly reduced overall survival, independently of other prognostic variables. In summary, this work reveals HOXA9 as a novel direct regulator of HOTAIR , and establishes HOTAIR as an independent prognostic marker, providing new therapeutic opportunities to treat this highly aggressive cancer.
dc.formatElectronic-eCollection
dc.format.extent15740 - 15756
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleThe long non-coding RNA <i>HOTAIR</i> is transcriptionally activated by HOXA9 and is an independent prognostic marker in patients with malignant glioma.
dc.typeJournal Article
dcterms.dateAccepted2018-02-21
rioxxterms.versionofrecord10.18632/oncotarget.24597
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-03
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfOncotarget
pubs.issue21
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Glioma Team
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Glioma Team
pubs.publication-statusPublished
pubs.volume9
pubs.embargo.termsNot known
icr.researchteamGlioma Teamen_US
dc.contributor.icrauthorJones, Chrisen


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