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Downregulation of miR-130b~301b cluster is mediated by aberrant promoter methylation and impairs cellular senescence in prostate cancer

2017Journal article Open access
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dc.contributor.authorRamalho-Carvalho, João
dc.contributor.authorPinho dos Santos Graça, Maria Inês
dc.contributor.authorGomez, Antonio
dc.contributor.authorOliveira, Jorge
dc.contributor.authorHenrique, Rui
dc.contributor.authorEsteller, Manel
dc.contributor.authorJerónimo, Carmen
dc.date.accessioned2019-05-20T13:15:58Z
dc.date.available2019-05-20T13:15:58Z
dc.date.issued2017
dc.description.abstractNumerous DNA-damaging cellular stresses, including oncogene activation and DNA-damage response (DDR), may lead to cellular senescence. Previous observations linked microRNA deregulation with altered senescent patterns, prompting us to investigate whether epigenetic repression of microRNAs expression might disrupt senescence in prostate cancer (PCa) cells. Differential methylation mapping in prostate tissues was carried using Infinium HumanMethylation450 BeadChip. After validation of methylation and expression analyses in a larger series of prostate tissues, the functional role of the cluster miR-130b~301b was explored using in vitro studies testing cell viability, apoptosis, invasion and DNA damage in prostate cancer cell lines. Western blot and RT-qPCR were performed to support those observations. We found that the miR-130b~301b cluster directs epigenetic activation of cell cycle inhibitors required for DDR activation, thus stimulating the senescence-associated secretory phenotype (SASP). Furthermore, overexpression of miR-130b~301b cluster markedly reduced the malignant phenotype of PCa cells. Altogether, these data demonstrate that miR-130b~301b cluster overexpression might effectively induce PCa cell growth arrest through epigenetic regulation of proliferation-blocking genes and activation of cellular senescence.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationRamalho-Carvalho, J., Graça, I., Gomez, A., Oliveira, J., Henrique, R., Esteller, M., & Jerónimo, C. (2017). Downregulation of miR-130b~301b cluster is mediated by aberrant promoter methylation and impairs cellular senescence in prostate cancer. Journal of Hematology & Oncology, 10(1), 43. https://doi.org/10.1186/s13045-017-0415-1
dc.identifier.doi10.1186/s13045-017-0415-1pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.22/13747
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationPCT: PEst-UID/DTP/00776/2013pt_PT
dc.relationPOCI-01-0145-FEDER-006868pt_PT
dc.relation.publisherversionhttps://jhoonline.biomedcentral.com/articles/10.1186/s13045-017-0415-1pt_PT
dc.subjectmiR-130bpt_PT
dc.subjectCell Cyclept_PT
dc.subjectCell Line, Tumorpt_PT
dc.subjectCellular Senescencept_PT
dc.subjectDNA Damagept_PT
dc.subjectDNA Repairpt_PT
dc.subjectMicroRNAspt_PT
dc.subjectProstatic Neoplasmspt_PT
dc.subjectDNA Methylationpt_PT
dc.titleDownregulation of miR-130b~301b cluster is mediated by aberrant promoter methylation and impairs cellular senescence in prostate cancerpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/COMPETE/EXPL%2FBIM-ONC%2F0556%2F2012/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F71293%2F2010/PT
oaire.citation.issue1pt_PT
oaire.citation.startPage43pt_PT
oaire.citation.titleJournal of Hematology and Oncologypt_PT
oaire.citation.volume10pt_PT
oaire.fundingStreamCOMPETE
oaire.fundingStreamSFRH
person.familyNamePinho dos Santos Graça
person.givenNameMaria Inês
person.identifier.orcid0000-0003-1383-4242
person.identifier.scopus-author-id6505981373
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
relation.isAuthorOfPublication8316e6ce-cc0a-41e6-90ab-910c93868670
relation.isAuthorOfPublication.latestForDiscovery8316e6ce-cc0a-41e6-90ab-910c93868670
relation.isProjectOfPublication478fe43f-88ae-4117-9f23-2a8f379f7c56
relation.isProjectOfPublicationa7c6b45b-cce6-48c1-adc0-0f12c04cad73
relation.isProjectOfPublication.latestForDiscovery478fe43f-88ae-4117-9f23-2a8f379f7c56

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