Open AccessEpigenetic regulation of EFEMP 1 in prostate cancer: biological relevance and clinical potential
Author(s) -
Almeida Mafalda,
Costa Vera L.,
Costa Natália R.,
RamalhoCarvalho João,
Baptista Tiago,
Ribeiro Franclim R.,
Paulo Paula,
Teixeira Manuel R.,
Oliveira Jorge,
Lothe Ragnhild A.,
Lind Guro E.,
Henrique Rui,
Jerónimo Carmen
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12394
Subject(s) - epigenetics , biology , carcinogenesis , prostate cancer , dna methylation , cancer research , methylation , histone , cancer , gene expression , gene , genetics
Epigenetic alterations are common in prostate cancer ( PC a) 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 EFEMP 1 as biomarker for PC a, unveiling its biological relevance in prostate carcinogenesis. Microarray analyses of treated PC a cell lines and primary tissues enabled the selection of differentially methylated genes, among which EFEMP 1 was further validated by MSP and bisulfite sequencing. Assessment of biomarker performance was accomplished by q MSP . Expression analysis of EFEMP 1 and characterization of histone marks were performed in tissue samples and cancer cell lines to determine the impact of epigenetic mechanisms on EFEMP 1 transcriptional regulation. Phenotypic assays, using transfected cell lines, permitted the evaluation of EFEMP 1 's role in PC a development. EFEMP 1 methylation assay discriminated PC a from normal prostate tissue ( NPT ; P < 0.001, K ruskall– W allis test) and renal and bladder cancers (96% sensitivity and 98% specificity). EFEMP 1 t ranscription levels inversely correlated with promoter methylation and histone deacetylation, suggesting that both epigenetic mechanisms are involved in gene regulation. Phenotypic assays showed that EFEMP 1 de novo expression reduces malignant phenotype of PC a cells. EFEMP 1 promoter methylation is prevalent in PC a and accurately discriminates PC a 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.