Epigenetic regulation of EFEMP1 in prostate cancer: biological relevance and clinical potential. Issue 11 (11th September 2014)

• Record Type: Journal Article
• Authors: Almeida, Mafalda; Costa, Vera L.; Costa, Natália R.; Ramalho‐Carvalho, João; Baptista, Tiago; Ribeiro, Franclim R.; Paulo, Paula; Teixeira, Manuel R.; Oliveira, Jorge; Lothe, Ragnhild A.; Lind, Guro E.; Henrique, Rui; Jerónimo, Carmen
• Is Part Of: Journal of cellular and molecular medicine. Volume 18:Issue 11(2014)
• Page Start: 2287
• Page End: 2297
• Publication Date: 2014-09-11
• Subjects: Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.12394
• Languages: English
• ISSNs: 1582-1838

Abstract

<abstract abstract-type="main" id="jcmm12394-abs-0001"> <title>Abstract</title> <p>Epigenetic alterations are common in prostate cancer (PCa) and seem to contribute decisively to its initiation and progression. Moreover, aberrant promoter methylation is a promising biomarker for non‐invasive screening. Herein, we sought to characterize EFEMP1 as biomarker for PCa, unveiling its biological relevance in prostate carcinogenesis. Microarray analyses of treated PCa cell lines and primary tissues enabled the selection of differentially methylated genes, among which <italic>EFEMP1</italic> was further validated by MSP and bisulfite sequencing. Assessment of biomarker performance was accomplished by qMSP. Expression analysis of <italic>EFEMP1</italic> and characterization of histone marks were performed in tissue samples and cancer cell lines to determine the impact of epigenetic mechanisms on <italic>EFEMP1</italic> transcriptional regulation. Phenotypic assays, using transfected cell lines, permitted the evaluation of <italic>EFEMP1</italic>'s role in PCa development. <italic>EFEMP1</italic> methylation assay discriminated PCa from normal prostate tissue (NPT;<italic> P</italic> < 0.001, Kruskall–Wallis test) and renal and bladder cancers (96% sensitivity and 98% specificity). <italic>EFEMP1 t</italic>ranscription levels inversely correlated with promoter methylation and histone deacetylation, suggesting that both epigenetic mechanisms are involved in gene regulation. Phenotypic assays showed that <italic>EFEMP1 de novo</italic> expression reduces malignant phenotype of PCa cells. <italic>EFEMP1</italic> promoter methylation is prevalent in PCa and accurately discriminates PCa from non‐cancerous prostate tissues and other urological neoplasms. This epigenetic alteration occurs early in prostate carcinogenesis and, in association with histone deacetylation, progressively leads to gene down‐regulation, fostering cell proliferation, invasion and evasion of apoptosis.</p> </abstract>