Browsing by Author "Pereira-Silva, Eva"
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- Epigenetic modulators as therapeutic targets in prostate cancerPublication . Pinho dos Santos Graça, Maria Inês; Pereira-Silva, Eva; Henrique, Rui; Packham, Graham; Crabb, Simon J.; Jerónimo, CarmenProstate cancer is one of the most common non-cutaneous malignancies among men worldwide. Epigenetic aberrations, including changes in DNA methylation patterns and/or histone modifications, are key drivers of prostate carcinogenesis. These epigenetic defects might be due to deregulated function and/or expression of the epigenetic machinery, affecting the expression of several important genes. Remarkably, epigenetic modifications are reversible and numerous compounds that target the epigenetic enzymes and regulatory proteins were reported to be effective in cancer growth control. In fact, some of these drugs are already being tested in clinical trials. This review discusses the most important epigenetic alterations in prostate cancer, highlighting the role of epigenetic modulating compounds in pre-clinical and clinical trials as potential therapeutic agents for prostate cancer management.
- Histone methyltransferase PRMT6 plays an oncogenic role of in prostate cancerPublication . Almeida-Rios, Diogo; Pinho dos Santos Graça, Maria Inês; Quintela Vieira, Ana Filipa; Ramalho-Carvalho, João; Pereira-Silva, Eva; Martins, Ana Teresa; Oliveira, Jorge; Gonçalves, Céline S.; Costa, Bruno M.; Henrique, Rui; Jerónimo, CarmenProstate cancer (PCa) is a major cause of morbidity and mortality. Until now the specific role of histone methyltransferases (HMTs) deregulated expression/activity in PCa is poorly understood. Herein we aimed to uncover the potential oncogenic role of PRMT6 in prostate carcinogenesis. PRMT6 overexpression was confirmed in PCa, at transcript and protein level. Stable PRMT6 knockdown in PC-3 cells attenuated malignant phenotype, increasing apoptosis and decreasing cell viability, migration and invasion. PRMT6 silencing was associated with decreased H3R2me2a levels and increased MLL and SMYD3 expression. PRMT6 silencing increased p21, p27 and CD44 and decreased MMP-9 expression and was associated with PI3K/AKT/mTOR downregulation and increased AR signaling pathway. In Sh-PRMT6 cells, AR restored expression might re-sensitized cells to androgen deprivation therapy, impacting in clinical management of castration-resistant PCa (CRPC). PRMT6 plays an oncogenic role in PCa and predicts for more clinically aggressive disease, constituting a potential target for patients with CRPC.