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Possible role of hsa-miR-194-5p, via regulation of HS3ST2 , in the pathogenesis of atopic dermatitis in children

European Journal of Dermatology(2020)

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Abstract
Background Atopic dermatitis (AD) is a prevalent inflammatory skin disease. Ample evidence has shown that non-coding RNAs play important roles in the progression of AD, however, the function of plasma microRNAs in AD is poorly understood. Objectives To identify key plasma microRNAs and explore their potential roles in AD. Materials and Methods Plasma microRNAs from five children with AD and five control children were sequenced by microRNA sequencing (miRNA-seq) and five differentially expressed microRNAs were verified by RT-qPCR in 30 AD and 15 control children. The most differentially expressed microRNA, hsa-miR-194-5p, was selected for further analysis. Human epidermal keratinocytes were subjected to RNA sequencing following over-expression of hsa-miR-194-5p, and down-regulated genes were detected by RT-qPCR. The diagnostic potential of hsa-miR-194-5p in AD was evaluated based on receiver operating characteristic (ROC) curve analysis. Further hsa-miR-194-5p-regulated expression and gene-hsa-miR-194-5p interactions were evaluated by western blotting and luciferase assays, respectively. Results We identified 40 differentially expressed microRNAs, 26 up-regulated and 14 down-regulated, in children with AD compared with controls. Among the five verified plasma microRNAs, the most significant change was down-regulated hsa-miR-194-5p, which was shown to potentially serve as a biomarker for AD based on ROC analysis. Twenty-two down-regulated genes were observed following hsa-miR-194-5p over-expression, which were significantly associated with keratinocyte differentiation and establishment of the skin barrier. Moreover, HS3ST2 protein expression was down-regulated following over-expression of hsa-miR-194-5p, and the 3′-UTR of HS3ST2 was shown to bind to hsa-miR-194-5p. Conclusion Hsa-miR-194-5p might be involved in the pathogenesis of AD by regulating HS3ST2 expression.
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Key words
atopic dermatitis,HS3ST2,hsa-miR-194-5p,microRNAs,sequence
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