MicroRNA-375 plays a dual role in prostate carcinogenesis
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/40236 |
Resumo: | Background: 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, aswellaswithregionallymph nodesmetastases. 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. |
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MicroRNA-375 plays a dual role in prostate carcinogenesisProstate cancerMicroRNAsEpigeneticsmiR-375CCND2Ciências Médicas::Medicina ClínicaScience & TechnologyBackground: 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, aswellaswithregionallymph nodesmetastases. 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.Research Center of Portuguese Oncology Institute - Porto (CI-IPOP 4–2012) and by the Federal funds through Programa Operacional Temático Factores de Competitividade (COMPETE) with co-participation from the European Community Fund (FEDER) and by the National funds through Fundação para a Ciência e Tecnología (FCT) under the projects EXPL/BIM-ONC/0556/2012. FQV and JRC were or are supported by FCT-Fundação para a Ciência e a Tecnologia grants (SFRH/BD/70564/2010 and SFRH/BD/71293/2010, respectively).BioMed Central (BMC)Universidade do MinhoCosta-Pinheiro, PedroRamalho-Carvalho, JoãoVieira, Filipa QuintelaTorres-Ferreira, JorgeOliveira, JorgeGonçalves, Céline S.Costa, Bruno MarquesHenrique, RuiJerónimo, Carmen2015-042015-04-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/40236engCosta-Pinheiro, P., Ramalho-Carvalho, J., et. al.(2015). MicroRNA-375 plays a dual role in prostate carcinogenesis. Clinical epigenetics, 7(1), 1.1868-708310.1186/s13148-015-0076-2http://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-015-0076-2info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:13:35Zoai:repositorium.sdum.uminho.pt:1822/40236Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:05:43.757398Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
MicroRNA-375 plays a dual role in prostate carcinogenesis |
title |
MicroRNA-375 plays a dual role in prostate carcinogenesis |
spellingShingle |
MicroRNA-375 plays a dual role in prostate carcinogenesis Costa-Pinheiro, Pedro Prostate cancer MicroRNAs Epigenetics miR-375 CCND2 Ciências Médicas::Medicina Clínica Science & Technology |
title_short |
MicroRNA-375 plays a dual role in prostate carcinogenesis |
title_full |
MicroRNA-375 plays a dual role in prostate carcinogenesis |
title_fullStr |
MicroRNA-375 plays a dual role in prostate carcinogenesis |
title_full_unstemmed |
MicroRNA-375 plays a dual role in prostate carcinogenesis |
title_sort |
MicroRNA-375 plays a dual role in prostate carcinogenesis |
author |
Costa-Pinheiro, Pedro |
author_facet |
Costa-Pinheiro, Pedro Ramalho-Carvalho, João Vieira, Filipa Quintela Torres-Ferreira, Jorge Oliveira, Jorge Gonçalves, Céline S. Costa, Bruno Marques Henrique, Rui Jerónimo, Carmen |
author_role |
author |
author2 |
Ramalho-Carvalho, João Vieira, Filipa Quintela Torres-Ferreira, Jorge Oliveira, Jorge Gonçalves, Céline S. Costa, Bruno Marques Henrique, Rui Jerónimo, Carmen |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Costa-Pinheiro, Pedro Ramalho-Carvalho, João Vieira, Filipa Quintela Torres-Ferreira, Jorge Oliveira, Jorge Gonçalves, Céline S. Costa, Bruno Marques Henrique, Rui Jerónimo, Carmen |
dc.subject.por.fl_str_mv |
Prostate cancer MicroRNAs Epigenetics miR-375 CCND2 Ciências Médicas::Medicina Clínica Science & Technology |
topic |
Prostate cancer MicroRNAs Epigenetics miR-375 CCND2 Ciências Médicas::Medicina Clínica Science & Technology |
description |
Background: 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, aswellaswithregionallymph nodesmetastases. 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. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-04 2015-04-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/40236 |
url |
http://hdl.handle.net/1822/40236 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Costa-Pinheiro, P., Ramalho-Carvalho, J., et. al.(2015). MicroRNA-375 plays a dual role in prostate carcinogenesis. Clinical epigenetics, 7(1), 1. 1868-7083 10.1186/s13148-015-0076-2 http://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-015-0076-2 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
BioMed Central (BMC) |
publisher.none.fl_str_mv |
BioMed Central (BMC) |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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