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MicroRNA-375 plays a dual role in prostate carcinogenesis

dc.contributor.authorCosta-Pinheiro, Pedro
dc.contributor.authorRamalho-Carvalho, João
dc.contributor.authorQuintela Vieira, Ana Filipa
dc.contributor.authorFerreira, Jorge
dc.contributor.authorOliveira, Jorge
dc.contributor.authorGonçalves, Céline S
dc.contributor.authorCosta, Bruno M .
dc.contributor.authorHenrique, Rui
dc.contributor.authorJeronimo, Carmen
dc.date.accessioned2015-06-04T08:31:53Z
dc.date.available2015-06-04T08:31:53Z
dc.date.issued2015
dc.description.abstractBackground: Prostate cancer (PCa), a highly incident and heterogeneous malignancy, mostly affects men from developed countries. Increased knowledge of the biological mechanisms underlying PCa onset and progression are critical for improved clinical management. MicroRNAs (miRNAs) deregulation is common in human cancers, and understanding how it impacts in PCa is of major importance. MiRNAs are mostly downregulated in cancer, although some are overexpressed, playing a critical role in tumor initiation and progression. We aimed to identify miRNAs overexpressed in PCa and subsequently determine its impact in tumorigenesis. Results: MicroRNA expression profiling in primary PCa and morphological normal prostate (MNPT) tissues identified 17 miRNAs significantly overexpressed in PCa. Expression of three miRNAs, not previously associated with PCa, was subsequently assessed in large independent sets of primary tumors, in which miR-182 and miR-375 were validated, but not miR-32. Significantly higher expression levels of miR-375 were depicted in patients with higher Gleason score and more advanced pathological stage, as well as with regional lymph nodes metastases. Forced expression of miR-375 in PC-3 cells, which display the lowest miR-375 levels among PCa cell lines, increased apoptosis and reduced invasion ability and cell viability. Intriguingly, in 22Rv1 cells, which displayed the highest miR-375 expression, knockdown experiments also attenuated the malignant phenotype. Gene ontology analysis implicated miR-375 in several key pathways deregulated in PCa, including cell cycle and cell differentiation. Moreover, CCND2 was identified as putative miR-375 target in PCa, confirmed by luciferase assay. Conclusions: A dual role for miR-375 in prostate cancer progression is suggested, highlighting the importance of cellular context on microRNA targeting.por
dc.identifier.citationCosta-Pinheiro, P., Ramalho-Carvalho, J., Quintela Vieira, A. F., Ferreira, J., Oliveira, J., Gonçalves, C. S., Costa, B. M., Henrique, R., & Jeronimo, C. (2015). MicroRNA-375 plays a dual role in prostate carcinogenesis. Clinical Epigenetics, 1–14. https://doi.org/10.1186/s13148-015-0076-2
dc.identifier.doi10.1186/s13148-015-0076-2
dc.identifier.urihttp://hdl.handle.net/10400.22/6219
dc.language.isoengpor
dc.peerreviewedyespor
dc.relation.publisherversionhttp://www.biomedcentral.com/content/pdf/s13148-015-0076-2.pdfpor
dc.subjectProstate cancerpor
dc.subjectMicroRNAspor
dc.subjectEpigeneticspor
dc.subjectmiR-375por
dc.subjectCCND2por
dc.titleMicroRNA-375 plays a dual role in prostate carcinogenesispor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage14por
oaire.citation.startPage1por
oaire.citation.titleClinical Epigeneticspor
person.familyNameQuintela Vieira
person.givenNameAna Filipa
person.identifier.orcid0000-0003-0130-7664
rcaap.rightsopenAccesspor
rcaap.typearticlepor
relation.isAuthorOfPublication47123d10-a0ed-47cc-a751-721489a13446
relation.isAuthorOfPublication.latestForDiscovery47123d10-a0ed-47cc-a751-721489a13446

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