SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3
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/1822/40545 |
Resumo: | Prostate cancer (PCa) is one of the most incident cancers worldwide but clinical and pathological parameters have limited ability to discriminate between clinically significant and indolent PCa. Altered expression of histone methyltransferases and histone methylation patterns are involved in prostate carcinogenesis. SMYD3 transcript levels have prognostic value and discriminate among PCa with different clinical aggressiveness, so we decided to investigate its putative oncogenic role on PCa.We silenced SMYD3 and assess its impact through in vitro (cell viability, cell cycle, apoptosis, migration, invasion assays) and in vivo (tumor formation, angiogenesis). We evaluated SET domain's impact in PCa cells' phenotype. Histone marks deposition on SMYD3 putative target genes was assessed by ChIP analysis.Knockdown of SMYD3 attenuated malignant phenotype of LNCaP and PC3 cell lines. Deletions affecting the SET domain showed phenotypic impact similar to SMYD3 silencing, suggesting that tumorigenic effect is mediated through its histone methyltransferase activity. Moreover, CCND2 was identified as a putative target gene for SMYD3 transcriptional regulation, through trimethylation of H4K20.Our results support a proto-oncogenic role for SMYD3 in prostate carcinogenesis, mainly due to its methyltransferase enzymatic activity. Thus, SMYD3 overexpression is a potential biomarker for clinically aggressive disease and an attractive therapeutic target in PCa. |
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SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3SMYD3Prostate cancerHistone methyltransferaseSET domainCyclin D2Ciências Médicas::Medicina BásicaScience & TechnologyProstate cancer (PCa) is one of the most incident cancers worldwide but clinical and pathological parameters have limited ability to discriminate between clinically significant and indolent PCa. Altered expression of histone methyltransferases and histone methylation patterns are involved in prostate carcinogenesis. SMYD3 transcript levels have prognostic value and discriminate among PCa with different clinical aggressiveness, so we decided to investigate its putative oncogenic role on PCa.We silenced SMYD3 and assess its impact through in vitro (cell viability, cell cycle, apoptosis, migration, invasion assays) and in vivo (tumor formation, angiogenesis). We evaluated SET domain's impact in PCa cells' phenotype. Histone marks deposition on SMYD3 putative target genes was assessed by ChIP analysis.Knockdown of SMYD3 attenuated malignant phenotype of LNCaP and PC3 cell lines. Deletions affecting the SET domain showed phenotypic impact similar to SMYD3 silencing, suggesting that tumorigenic effect is mediated through its histone methyltransferase activity. Moreover, CCND2 was identified as a putative target gene for SMYD3 transcriptional regulation, through trimethylation of H4K20.Our results support a proto-oncogenic role for SMYD3 in prostate carcinogenesis, mainly due to its methyltransferase enzymatic activity. Thus, SMYD3 overexpression is a potential biomarker for clinically aggressive disease and an attractive therapeutic target in PCa.Liga Portuguesa Contra o Cancro – Núcleo Regional do Norte , Research Center of Portuguese Oncology Institute – Porto (CI-IPOP 4-2012) and European Community’s Seventh Framework Programme – Grant number FP7-HEALTH-F5-2009-241783. FQV and SS-S are supported by FCT-Fundação para a Ciência e a Tecnologia grants (SFRH/BD/70564/2010 and PTDC/ SAU-MET/113415/2009), IG is a Posdoc fellow from FCT (PEst-OE/SAU/UI0776/2014).Impact JournalsUniversidade do MinhoVieira, Filipa QuintelaCosta-Pinheiro, PedroAlmeida-Rios, DiogoGraça, InêsMonteiro-Reis, SaraSimões-Sousa, SusanaCarneiro, IsaSousa, Elsa JoanaInês Godinho, MariaBaltazar, FátimaHenrique, RuiJerónimo, Carmen2015-052015-05-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/40545engVieira, F. Q., Costa-Pinheiro, P., Almeida-Rios, D., Graça, I., et.al.(2015). SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3. Oncotarget, 6(15), 13644–136571949-255310.18632/oncotarget.376725980436http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=3767&path%5B%5D=8511info: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:RCAAP2023-07-21T12:09:17Zoai:repositorium.sdum.uminho.pt:1822/40545Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:00:40.165041Repositório 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 |
SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3 |
title |
SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3 |
spellingShingle |
SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3 Vieira, Filipa Quintela SMYD3 Prostate cancer Histone methyltransferase SET domain Cyclin D2 Ciências Médicas::Medicina Básica Science & Technology |
title_short |
SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3 |
title_full |
SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3 |
title_fullStr |
SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3 |
title_full_unstemmed |
SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3 |
title_sort |
SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3 |
author |
Vieira, Filipa Quintela |
author_facet |
Vieira, Filipa Quintela Costa-Pinheiro, Pedro Almeida-Rios, Diogo Graça, Inês Monteiro-Reis, Sara Simões-Sousa, Susana Carneiro, Isa Sousa, Elsa Joana Inês Godinho, Maria Baltazar, Fátima Henrique, Rui Jerónimo, Carmen |
author_role |
author |
author2 |
Costa-Pinheiro, Pedro Almeida-Rios, Diogo Graça, Inês Monteiro-Reis, Sara Simões-Sousa, Susana Carneiro, Isa Sousa, Elsa Joana Inês Godinho, Maria Baltazar, Fátima Henrique, Rui Jerónimo, Carmen |
author2_role |
author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Vieira, Filipa Quintela Costa-Pinheiro, Pedro Almeida-Rios, Diogo Graça, Inês Monteiro-Reis, Sara Simões-Sousa, Susana Carneiro, Isa Sousa, Elsa Joana Inês Godinho, Maria Baltazar, Fátima Henrique, Rui Jerónimo, Carmen |
dc.subject.por.fl_str_mv |
SMYD3 Prostate cancer Histone methyltransferase SET domain Cyclin D2 Ciências Médicas::Medicina Básica Science & Technology |
topic |
SMYD3 Prostate cancer Histone methyltransferase SET domain Cyclin D2 Ciências Médicas::Medicina Básica Science & Technology |
description |
Prostate cancer (PCa) is one of the most incident cancers worldwide but clinical and pathological parameters have limited ability to discriminate between clinically significant and indolent PCa. Altered expression of histone methyltransferases and histone methylation patterns are involved in prostate carcinogenesis. SMYD3 transcript levels have prognostic value and discriminate among PCa with different clinical aggressiveness, so we decided to investigate its putative oncogenic role on PCa.We silenced SMYD3 and assess its impact through in vitro (cell viability, cell cycle, apoptosis, migration, invasion assays) and in vivo (tumor formation, angiogenesis). We evaluated SET domain's impact in PCa cells' phenotype. Histone marks deposition on SMYD3 putative target genes was assessed by ChIP analysis.Knockdown of SMYD3 attenuated malignant phenotype of LNCaP and PC3 cell lines. Deletions affecting the SET domain showed phenotypic impact similar to SMYD3 silencing, suggesting that tumorigenic effect is mediated through its histone methyltransferase activity. Moreover, CCND2 was identified as a putative target gene for SMYD3 transcriptional regulation, through trimethylation of H4K20.Our results support a proto-oncogenic role for SMYD3 in prostate carcinogenesis, mainly due to its methyltransferase enzymatic activity. Thus, SMYD3 overexpression is a potential biomarker for clinically aggressive disease and an attractive therapeutic target in PCa. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-05 2015-05-01T00:00:00Z |
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/1822/40545 |
url |
http://hdl.handle.net/1822/40545 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Vieira, F. Q., Costa-Pinheiro, P., Almeida-Rios, D., Graça, I., et.al.(2015). SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3. Oncotarget, 6(15), 13644–13657 1949-2553 10.18632/oncotarget.3767 25980436 http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=3767&path%5B%5D=8511 |
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info:eu-repo/semantics/openAccess |
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openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Impact Journals |
publisher.none.fl_str_mv |
Impact Journals |
dc.source.none.fl_str_mv |
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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) |
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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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