Repository logo
 
Publication

A novel molecular link between HOXA9 and WNT6 in glioblastoma identifies a subgroup of patients with particular poor prognosis

2020Journal article Open access
Simple item page
dc.contributor.authorGonçalves, Céline S.
dc.contributor.authorXavier‐Magalhães, Ana
dc.contributor.authorMartins, Eduarda P.
dc.contributor.authorPinto, Afonso A.
dc.contributor.authorPires, Manuel
dc.contributor.authorPinheiro, Célia
dc.contributor.authorReis, Rui M.
dc.contributor.authorSousa, Nuno
dc.contributor.authorCosta, Bruno M.
dc.date.accessioned2022-03-31T10:38:23Z
dc.date.available2022-03-31T10:38:23Z
dc.date.issued2020
dc.description.abstractDespite much effort to improve treatments, patients with malignant glioma still present a very poor prognosis that has not changed significantly in the last decades. In this context, it is crucial to better understand glioma pathogenesis to identify new molecular prognostic subgroups and therapeutic targets. WNT6 was recently identified as a new oncogenic molecule in glioblastoma (GBM), with prognostic value in patients, but the mechanisms underlying WNT6 aberrant expression in glioma are still unknown. WNT6 was overexpressed in a subset of gliomas independently of IDH mutations, 1p/19q codeletion status, and WNT6 gene copy number. Interestingly, WNT6 expression is associated with the DNA methylation levels of particular CpG regions at both the WNT6 promoter and the gene body in glioma patient samples. HOXA9, a transcription factor previously associated with poorer clinical outcome in GBM, was identified as a novel transcriptional regulator of WNT6, activating the WNT/β-catenin pathway in vitro and in vivo. In various cohorts of glioma patients, mRNA levels of WNT6 and HOXA9 were significantly correlated, extending our in vitro and in vivo findings into the clinical setting. Interestingly, this novel molecular link between WNT6 and HOXA9 was not limited to glioma, as they were co-expressed also in patients with other tumor types. Clinically, WNT6 was a prognostic biomarker of shorter survival in GBM, independently of HOXA9 expression. Concomitant high expression of both WNT6 and HOXA9 identified a subgroup of patients with particularly dismal survival. These findings describe novel WNT6 regulatory mechanisms in GBM, establishing particular DNA methylation patterns and HOXA9 as critical regulators of WNT6 expression in glioma. This HOXA9-WNT6 molecular link supports WNT signaling in GBM cells and is a powerful prognostic biomarker, highlighting the clinical relevance of this axis in patients. Novel therapies targeting WNT6-HOXA9 signaling may thus be useful for this deadly disease.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationGonçalves CS, Xavier-Magalhães A, Martins EP, et al. A novel molecular link between HOXA9 and WNT6 in glioblastoma identifies a subgroup of patients with particular poor prognosis. Mol Oncol. 2020;14(6):1224-1241. doi:10.1002/1878-0261.12633pt_PT
dc.identifier.doi10.1002/1878-0261.12633pt_PT
dc.identifier.issn1574-7891
dc.identifier.issn1878-0261
dc.identifier.urihttp://hdl.handle.net/10400.16/2680
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherJohn Wiley & Sonspt_PT
dc.relationNORTE-01-0145-FEDER-000013pt_PT
dc.relationNORTE-01-0246-FEDER-000012pt_PT
dc.relationTranslating Mechanisms of Aggressiveness in Brain Tumors into Prognostic and Therapeutic Value: Insights from the Oncogenic HOXA9 Homeoprotein
dc.relationRelevance of HOTTIP in Glioblastoma: Molecular, Functional and Prognostic Insights
dc.relationROLES OF THE LONG NON-CODING RNA HOTAIR IN GLIOBLASTOMA: FUNCTIONAL, THERAPEUTIC AND PROGNOSTIC INSIGHTS
dc.relationNovel precision therapies exploiting the critical oncogenic molecule HOXA9 in malignant brain tumors
dc.relation.publisherversionhttps://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.12633pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectDNA methylationpt_PT
dc.subjectHOXpt_PT
dc.subjectWNT pathwaypt_PT
dc.subjectgliomapt_PT
dc.subjecthomeoboxpt_PT
dc.subjectregulationpt_PT
dc.titleA novel molecular link between HOXA9 and WNT6 in glioblastoma identifies a subgroup of patients with particular poor prognosispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleTranslating Mechanisms of Aggressiveness in Brain Tumors into Prognostic and Therapeutic Value: Insights from the Oncogenic HOXA9 Homeoprotein
oaire.awardTitleRelevance of HOTTIP in Glioblastoma: Molecular, Functional and Prognostic Insights
oaire.awardTitleROLES OF THE LONG NON-CODING RNA HOTAIR IN GLIOBLASTOMA: FUNCTIONAL, THERAPEUTIC AND PROGNOSTIC INSIGHTS
oaire.awardTitleNovel precision therapies exploiting the critical oncogenic molecule HOXA9 in malignant brain tumors
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FSAU-GMG%2F113795%2F2009/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Investigador FCT/IF%2F00601%2F2012%2FCP0177%2FCT0006/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/FARH/SFRH%2FBD%2F92786%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/FARH/SFRH%2FBD%2F88220%2F2012/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POR_NORTE/PD%2FBDE%2F143154%2F2019/PT
oaire.citation.conferencePlaceNetherlandspt_PT
oaire.citation.endPage1241pt_PT
oaire.citation.issue6pt_PT
oaire.citation.startPage1224pt_PT
oaire.citation.titleMolecular Oncologypt_PT
oaire.citation.volume14pt_PT
oaire.fundingStream5876-PPCDTI
oaire.fundingStreamInvestigador FCT
oaire.fundingStreamFARH
oaire.fundingStreamFARH
oaire.fundingStreamPOR_NORTE
person.familyNamePires
person.givenNameManuel
person.identifier.orcid0000-0002-0046-6455
person.identifier.scopus-author-id7102122793
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication07361da1-f095-4eb3-9856-a76e41bd21a6
relation.isAuthorOfPublication.latestForDiscovery07361da1-f095-4eb3-9856-a76e41bd21a6
relation.isProjectOfPublication10cff1f0-b40b-4bbe-af5c-c7ca94e993cb
relation.isProjectOfPublicatione8c711ac-10aa-4bdd-928d-58d9ef7f57e7
relation.isProjectOfPublicationcbdd2ef5-4409-42d5-af38-0f8fd2e5ed8b
relation.isProjectOfPublication61d5777d-bee0-4398-9f77-0348ee1601b0
relation.isProjectOfPublication82e8a0b9-d0a8-4215-8f9a-f774ac30ca6c
relation.isProjectOfPublication.latestForDiscovery10cff1f0-b40b-4bbe-af5c-c7ca94e993cb

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Goncalves-2020-A-novel-molecular-link-between-hoxa.pdf
Size:
2.81 MB
Format:
Adobe Portable Document Format
Download

Collections

SNP - Artigos publicados em revistas indexadas na Medline
SNC - Artigos publicados em revistas indexadas na Medline