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Mechanisms of human telomerase reverse transcriptase (hTERT) regulation: clinical impacts in cancer

dc.contributor.authorLeão, Ricardo
dc.contributor.authorApolónio, Joana
dc.contributor.authorLee, Donghyun
dc.contributor.authorFigueiredo, Arnaldo
dc.contributor.authorTabori, Uri
dc.contributor.authorCastelo-Branco, Pedro
dc.date.accessioned2018-04-04T09:06:23Z
dc.date.available2018-04-04T09:06:23Z
dc.date.issued2018-03-12
dc.date.updated2018-04-01T13:20:09Z
dc.description.abstractBackground Limitless self-renewal is one of the hallmarks of cancer and is attained by telomere maintenance, essentially through telomerase (hTERT) activation. Transcriptional regulation of hTERT is believed to play a major role in telomerase activation in human cancers. Main body The dominant interest in telomerase results from its role in cancer. The role of telomeres and telomere maintenance mechanisms is well established as a major driving force in generating chromosomal and genomic instability. Cancer cells have acquired the ability to overcome their fate of senescence via telomere length maintenance mechanisms, mainly by telomerase activation. hTERT expression is up-regulated in tumors via multiple genetic and epigenetic mechanisms including hTERT amplifications, hTERT structural variants, hTERT promoter mutations and epigenetic modifications through hTERT promoter methylation. Genetic (hTERT promoter mutations) and epigenetic (hTERT promoter methylation and miRNAs) events were shown to have clinical implications in cancers that depend on hTERT activation. Knowing that telomeres are crucial for cellular self-renewal, the mechanisms responsible for telomere maintenance have a crucial role in cancer diseases and might be important oncological biomarkers. Thus, rather than quantifying TERT expression and its correlation with telomerase activation, the discovery and the assessment of the mechanisms responsible for TERT upregulation offers important information that may be used for diagnosis, prognosis, and treatment monitoring in oncology. Furthermore, a better understanding of these mechanisms may promote their translation into effective targeted cancer therapies. Conclusion Herein, we reviewed the underlying mechanisms of hTERT regulation, their role in oncogenesis, and the potential clinical applications in telomerase-dependent cancers.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doihttp://dx.doi.org/10.1186/s12929-018-0422-8pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.1/10529
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherBioMed Centralpt_PT
dc.rights.holderThe Author(s).
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectTelomerespt_PT
dc.subjectTelomerasept_PT
dc.subjectTelomerase regulationpt_PT
dc.subjectCancer biomarkerspt_PT
dc.titleMechanisms of human telomerase reverse transcriptase (hTERT) regulation: clinical impacts in cancerpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FBIM%2F04773%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/PD/PD%2FBD%2F105899%2F2014/PT
oaire.citation.endPage22pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleJournal of Biomedical Sciencept_PT
oaire.citation.volume25pt_PT
oaire.fundingStream5876
oaire.fundingStreamPD
person.familyNameApolónio
person.familyNameCastelo-Branco
person.givenNameJoana
person.givenNamePedro
person.identifier.ciencia-id791E-9E39-2795
person.identifier.ciencia-idE015-7F8F-5CA1
person.identifier.orcid0000-0002-9727-1813
person.identifier.orcid0000-0002-3453-3978
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
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublicationbb25b5ad-1769-42be-a7d3-8fe76215aa23
relation.isAuthorOfPublication.latestForDiscovery01cf2be1-ea9f-4082-bcc6-e50fe4ad9fe1
relation.isProjectOfPublicatione13142f2-37b8-4b5a-b2cd-352e62003184
relation.isProjectOfPublication21aeef53-d47f-4fb9-bbad-f798159b2e70
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