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

被引:32
|
作者
Yooyongsatit, Surasak [1 ]
Ruchusatsawat, Kriangsak [2 ]
Noppakun, Nopadon [3 ]
Hirankarn, Nattiya [4 ]
Mutirangura, Apiwat [5 ]
Wongpiyabovorn, Jongkonnee [4 ]
机构
[1] Chulalongkorn Univ, Grad Sch, Interdisciplinary Program, Med Microbiol, Bangkok 10330, Thailand
[2] NIH, Dept Med Sci, Nonthaburi, Thailand
[3] Chulalongkorn Univ, Fac Med, Dept Med, Div Dermatol, Bangkok 10330, Thailand
[4] Chulalongkorn Univ, Fac Med, Ctr Excellence Immunol & Immune Mediated Dis, Dept Anat, Bangkok 10330, Thailand
[5] Chulalongkorn Univ, Fac Med, Ctr Excellence Mol Genet Canc & Human Dis, Dept Anat, Bangkok 10330, Thailand
关键词
P16(INK4A) GENE PROMOTER; DNA HYPOMETHYLATION; L1; RETROTRANSPOSON; CANCER; HYPERMETHYLATION; CPG; DIFFERENTIATION; ASSOCIATION; EPIDERMIS; TISSUES;
D O I
10.1038/jhg.2015.33
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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 %(CC)-C-u-C-u were prominent in the keratinocytes when compared with normal controls (P=0.014 and P=0.020, respectively). Alternatively, %(CC)-C-u-C-m 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 (CC)-C-u-C-u and (CC)-C-u-C-m 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 x 10(-27) and P=2.14 x 10(-21), respectively). Modification in LINE-1 methylation may alter the gene expression resulting in a phenotypic change of the psoriatic skin. %(CC)-C-u-C-u and %(CC)-C-u-C-m may be used as biomarkers for psoriasis.
引用
收藏
页码:349 / 355
页数:7
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