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Epigenetic disruption of miR-130a promotes prostate cancer by targeting SEC23B and DEPDC1

2017Journal article Restricted access
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dc.contributor.authorRamalho-Carvalho, João
dc.contributor.authorMartins, João Barbosa
dc.contributor.authorCekaite, Lina
dc.contributor.authorSveen, Anita
dc.contributor.authorTorres-Ferreira, Jorge
dc.contributor.authorPinho dos Santos Graça, Maria Inês
dc.contributor.authorCosta-Pinheiro, Pedro
dc.contributor.authorEilertsen, Ina Andrassy
dc.contributor.authorAntunes, Luís
dc.contributor.authorOliveira, Jorge
dc.contributor.authorLothe, Ragnhild A.
dc.contributor.authorHenrique, Rui
dc.contributor.authorJerónimo, Carmen
dc.date.accessioned2017-01-20T15:08:33Z
dc.date.available2017-01-20T15:08:33Z
dc.date.issued2017
dc.description.abstractMicroRNAs (miRNAs) are small, non-coding RNAs that mediate post-transcriptional gene silencing, fine tuning gene expression. In an initial screen, miRNAs were found to be globally down-regulated in prostate cancer (PCa) cell lines and primary tumors. Exposure of PCa cell lines to a demethylating agent, 5-Aza-CdR resulted in an increase in the expression levels of miRNAs in general. Using stringent filtering criteria miR-130a was identified as the most promising candidate and selected for validation analyses in our patient series. Down-regulation of miR-130a was associated with promoter hypermethylation. MiR-130a methylation levels discriminated PCa from non-malignant tissues (AUC=0.956), and urine samples revealed high specificity for non-invasive detection of patients with PCa (AUC=0.89). Additionally, repressive histone marks were also found in the promoter of miR-130a. Over-expression of miR-130a in PCa cells reduced cell viability and invasion capability, and increased apoptosis. Putative targets of miR-130a were assessed by microarray expression profiling and DEPD1C and SEC23B were selected for validation. Silencing of both genes resembled the effect of over-expressing miR-130a in PCa cells. Our data indicate that miR-130a is an epigenetically regulated miRNA involved in regulation of key molecular and phenotypic features of prostate carcinogenesis, acting as a tumor suppressor miRNA.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationRamalho-Carvalho, J., Martins, J. B., Cekaite, L., Sveen, A., Torres-Ferreira, J., Graça, I., Costa-Pinheiro, P., Eilertsen, I. A., Antunes, L., Oliveira, J., Lothe, R. A., Henrique, R., & Jerónimo, C. (2017). Epigenetic disruption of miR-130a promotes prostate cancer by targeting SEC23B and DEPDC1. Cancer Letters, 385, 150–159. https://doi.org/10.1016/j.canlet.2016.10.028
dc.identifier.doi10.1016/j.canlet.2016.10.028pt_PT
dc.identifier.issn0304-3835
dc.identifier.urihttp://hdl.handle.net/10400.22/9335
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S0304383516306498pt_PT
dc.subjectmiR's epigenetic regulationpt_PT
dc.subjectmiR-130apt_PT
dc.subjectmiRNApt_PT
dc.subjectProstate cancerpt_PT
dc.subjectSEC23Bpt_PT
dc.subjectDEPDC1pt_PT
dc.titleEpigenetic disruption of miR-130a promotes prostate cancer by targeting SEC23B and DEPDC1pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage159pt_PT
oaire.citation.startPage150pt_PT
oaire.citation.titleCancer Letterspt_PT
oaire.citation.volume385pt_PT
person.familyNamePinho dos Santos Graça
person.givenNameMaria Inês
person.identifier.orcid0000-0003-1383-4242
person.identifier.scopus-author-id6505981373
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication8316e6ce-cc0a-41e6-90ab-910c93868670
relation.isAuthorOfPublication.latestForDiscovery8316e6ce-cc0a-41e6-90ab-910c93868670

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