Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.22/6220
Título: SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3
Autor: Quintela Vieira, Ana Filipa
Costa-Pinheiro, Pedro
Almeida-Rios, Diogo
Pinho dos Santos Graça, Maria Inês
Reis, Sara
Simões-Sousa, Susana
Carneiro, Isa
Sousa, Elsa Joana
Godinho, Maria Inês
Baltazar, Fatima
Henrique, Rui
Jeronimo, Carmen
Palavras-chave: SMYD3
prostate cancer
histone methyltransferase
SET domain
cyclin D2
Data: 2015
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.
Peer review: yes
URI: http://hdl.handle.net/10400.22/6220
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