Epigenetic repression of HOXB cluster in oral cancer cell lines

被引:33
|
作者
Aquino Xavier, Flavia Calo [1 ,2 ]
de Souza Setubal Destro, Maria Fernanda [3 ]
Esteves Duarte, Carina Magalhaes [3 ]
Nunes, Fabio Daumas [3 ]
机构
[1] Univ Fed Bahia, Sch Dent, Dept Propaedeut, BR-40110150 Salvador, BA, Brazil
[2] Univ Fed Bahia, Sch Dent, Integrated Clin, BR-40110150 Salvador, BA, Brazil
[3] Univ Sao Paulo, Dept Estomatol, BR-05508000 Butanta Sao Paulo, SP, Brazil
基金
巴西圣保罗研究基金会;
关键词
DNA methylation; Epigenetics; Oral cancer; HOX genes; HOMEOBOX GENE-EXPRESSION; DE-NOVO METHYLATION; DNA METHYLATION; PROMOTER HYPERMETHYLATION; CARCINOMA TISSUES; BREAST-CANCER; CPG ISLANDS; OVEREXPRESSION; IDENTIFICATION; PATHWAY;
D O I
10.1016/j.archoralbio.2014.05.001
中图分类号
R78 [口腔科学];
学科分类号
1003 ;
摘要
Objective: Aberrant DNA methylation is a fundamental transcriptional control mechanism in carcinogenesis. The expression of homeobox genes is usually controlled by an epigenetic mechanism, such as the methylation of CpG islands in the promoter region. The aim of this study was to describe the differential methylation pattern of HOX genes in oral squamous cell carcinoma (OSCC) cell lines and transcript status in a group of hypermethylated and hypomethylated genes. Design: Quantitative analysis of DNA methylation was performed on two OSCC cell lines (SCC4 and SCC9) using a method denominated Human Homeobox Genes EpiTect Methyl qPCR Arrays, which allowed fast, precise methylation detection of 24 HOX specific genes without bisulfite conversion. Results: Methylation greater than 50% was detected in HOXA11, HOXA6, HOXA7, HOXA9, HOXB1, HOXB2, HOXB3, HOXB4, HOXB5, HOXB6, HOXC8 and HOXD10. Both cell lines demonstrated similar hypermethylation status for eight HOX genes. A similar pattern of promoter hypermethylation and hypomethylation was demonstrated for the HOXB cluster and HOXA cluster, respectively. Moreover, the hypermethylation profile of the HOXB cluster, especially HOXB4, was correlated with decreased transcript expression, which was restored following treatment with 5-aza-2'-deoxycytidine. Conclusions: The homeobox methylation profile in OSCC cell lines is consistent with an epigenetic biomarker. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:783 / 789
页数:7
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