Unregulated expression of histone methylases and demethylases in prostate cancer

Authors and affiliations:

Filipa Quintela Vieira1,2, Pedro Costa-Pinheiro1, João Ramalho-Carvalho1, Andreia Pereira1, Francisco Duarte Menezes3, Luís Antunes4, Isa Carneiro1,3, Jorge Oliveira5, Rui Henrique 1,3,6*, Carmen Jerónimo 1,6*#

1.Cancer Epigenetics Group – Research Center, Portuguese Oncology Institute – Porto, Portugal; 2.School of Allied Health Sciences (ESTSP), Polytechnic of Porto, Portugal; Departments of 3.Pathology, 4.Epidemiology and 5Urology – Portuguese Oncology Institute – Porto, Portugal; 6.Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS) – University of Porto, Portugal

#Joint senior authors

Abstract:

Prostate cancer (PCa), a leading cause of cancer-related morbidity and mortality, arises through the acquisition of genetic and epigenetic alterations. Deregulation of histone methyltransferases (HMTs) or demethylases (HDMs) has been associated with PCa development and progression. However, the precise influence of altered HMTs or HDMs expression and respective histone marks in PCa onset and progression remains largely unknown. To clarify the role of HMTs and HDMs in prostate carcinogenesis, expression levels of 37 HMTs and 20 HDMs were assessed in normal prostate and PCa tissue samples by RT-qPCR. SMYD3, SUV39H2, PRMT6, KDM5A and KDM6A were up-regulated, whereas MLL1-5 and KDM4B were downregulated in PCa, compared to normal prostate tissues. Remarkably, PRMT6 was the histone modifier that best discriminated normal from tumorous tissue samples. Interestingly, EZH2 and SMYD3 expression levels significantly correlated with less differentiated and more aggressive tumors. Remarkably, SMYD3 expression levels were of independent prognostic value for prediction of disease-specific survival of PCa patients with clinically localized disease submitted to radical prostatectomy. We concluded that expression profiling of HMTs and HDMs, especially SMYD3, might be of clinical usefulness for assessment of PCa patients and assist in pre-therapeutic decision-making.

Journal:
Endocrine-related Cancer

Link:
http://www.ncbi.nlm.nih.gov/pubmed/24200674