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寻常型银屑病患者角质形成细胞中LINE-1和Alu甲基化的模式及功能作用

Patterns and functional roles of LINE-1 and Alu methylation in the keratinocyte from patients with psoriasis vulgaris.

作者信息

Yooyongsatit Surasak, Ruchusatsawat Kriangsak, Noppakun Nopadon, Hirankarn Nattiya, Mutirangura Apiwat, Wongpiyabovorn Jongkonnee

机构信息

Medical Microbiology, Interdisciplinary Program, Graduate School Chulalongkorn University, Bangkok, Thailand.

National Institute of Health, Department of Medical Sciences, Nontaburi, Thailand.

出版信息

J Hum Genet. 2015 Jul;60(7):349-55. doi: 10.1038/jhg.2015.33. Epub 2015 Apr 2.

Abstract

Alterations in LINE-1 methylation are related to many diseases. The levels and patterns of LINE-1 hypomethylation were associated with a higher risk in developing several cancers, having a poorer prognosis and more aggressiveness. To evaluate the LINE-methylated status in psoriasis, LINE-1 methylation in various cells from patients with psoriasis, squamous cell carcinoma and normal controls were assessed by combined bisulfite restriction analysis of LINE-1. The results of the epigenetic changes for intragenic LINE-1 gene expression were also tested on two known expression microarrays. In patients with psoriasis, hypomethylation of LINE-1 and increase in %(u)C(u)C were prominent in the keratinocytes when compared with normal controls (P=0.014 and P=0.020, respectively). Alternatively, %(u)C(m)C was significantly lower in patients with severe psoriasis compared with mild psoriasis (P=0.022). The receiver-operating characteristic curve analysis indicated the high specificity and sensitivity of (u)C(u)C and (u)C(m)C in detecting psoriasis and severity of psoriasis. From expression array analysis, genes with LINE-1 were downregulated more than those genes without LINE-1 (P=3.84 × 10(-27) and P=2.14 × 10(-21), respectively). Modification in LINE-1 methylation may alter the gene expression resulting in a phenotypic change of the psoriatic skin. %(u)C(u)C and %(u)C(m)C may be used as biomarkers for psoriasis.

摘要

LINE-1甲基化的改变与多种疾病相关。LINE-1低甲基化的水平和模式与多种癌症发生风险较高、预后较差及侵袭性更强有关。为评估银屑病中LINE甲基化状态,通过LINE-1的联合亚硫酸氢盐限制性分析,对银屑病患者、鳞状细胞癌患者及正常对照者的各种细胞中的LINE-1甲基化进行了评估。还在两个已知的表达微阵列上测试了基因内LINE-1基因表达的表观遗传变化结果。与正常对照相比,银屑病患者角质形成细胞中LINE-1低甲基化及%(u)C(u)C增加显著(分别为P = 0.014和P = 0.020)。另外,重度银屑病患者的%(u)C(m)C显著低于轻度银屑病患者(P = 0.022)。受试者工作特征曲线分析表明,%(u)C(u)C和%(u)C(m)C在检测银屑病及银屑病严重程度方面具有高特异性和敏感性。从表达阵列分析来看,含LINE-1的基因下调程度大于不含LINE-1的基因(分别为P = 3.84×10(-27)和P = 2.14×10(-21))。LINE-1甲基化修饰可能会改变基因表达,导致银屑病皮肤出现表型变化。%(u)C(u)C和%(u)C(m)C可用作银屑病的生物标志物。

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