The involvement of CHD5 hypermethylation in laryngeal squamous cell carcinoma

被引:45
作者
Wang, Jin [1 ,2 ]
Chen, Hong [1 ]
Fu, Shuang [1 ]
Xu, Zhen-Ming [3 ]
Sun, Kai-Lai [1 ]
Fu, Wei-Neng [1 ]
机构
[1] China Med Univ, Dept Med Genet, Shenyang 110001, Peoples R China
[2] China Med Univ, Shengjing Hosp, ENT Dept, Shenyang 110004, Peoples R China
[3] 463 Hosp Chinese PLA, ENT Dept, Shenyang 110042, Peoples R China
关键词
CHD5; Hypermethylation; Laryngeal squamous cell carcinoma; Immunohistochemistry; Sequencing; Apoptosis; TUMOR-SUPPRESSOR GENE; DNA METHYLATION; BREAST-CANCER; PROMOTER; HEAD; NEUROBLASTOMAS; EXPRESSION; 1P36.31;
D O I
10.1016/j.oraloncology.2011.05.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Chromodomain helicase DNA-binding protein 5 (CHD5) has been found to be a candidate tumor suppressor gene (TSG) in malignant neural tumors. In mice heterozygous for chd5 deficiency, the first tumor observed was pathological squamous cell carcinoma. More than 95% of primary laryngeal cancer is squamous cell carcinoma. Thus, we explored the expression of CHD5 in 65 patients with laryngeal squamous cell carcinoma (LSCC) using real-time PCR, immunohistochemistry and Western blotting. DNA methylation was detected using bisulfate-specific sequencing. The potential function of CHD5 was determined using MTT, apoptosis and transwell migration assays in CHD5-transfected Hep-2 cells. Our results revealed that the mRNA and protein expression levels of CHD5 in LSCC tissues were significantly lower than those in clear surgical margin tissues (p < 0.05), and there is a significant correlation between the mRNA and protein expression levels of CHD5 (p < 0.01). In addition, there were significant differences in CHD5 mRNA and protein levels with respect to the patient's clinical stage (p < 0.05). Aberrant methylation of the CHD5 promoter was frequently found in the Hep-2 cell line and LSCC tumor tissues, especially tumor tissues from advanced TNM (p < 0.05) or older patients (p < 0.05). Finally, ectopic expression of CHD5 in laryngeal cancer cells led to significant inhibition of growth and invasiveness. Our data suggest that CHD5 is a tumor suppressor gene that is epigenetically downregulated in LSCC. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:601 / 608
页数:8
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