Department of Genetics, Washington University School of Medicine, St Louis, MO 63110, USA.
Hum Mol Genet. 2011 Oct 15;20(20):4025-40. doi: 10.1093/hmg/ddr331. Epub 2011 Aug 1.
Psoriasis is a chronic and complex inflammatory skin disease with lesions displaying dramatically altered mRNA expression profiles. However, much less is known about the expression of small RNAs. Here, we describe a comprehensive analysis of the normal and psoriatic skin miRNAome with next-generation sequencing in a large patient cohort. We generated 6.7 × 10(8) small RNA reads representing 717 known and 284 putative novel microRNAs (miRNAs). We also observed widespread expression of isomiRs and miRNAs derived from known and novel miRNA loci, and a low frequency of miRNA editing in normal and psoriatic skin. The expression and processing of selected novel miRNAs were confirmed with qRT-PCR in skin and other human tissues or cell lines. Eighty known and 18 novel miRNAs were 2-42-fold differentially expressed in psoriatic skin. Of particular significance was the 2.7-fold upregulation of a validated novel miRNA derived from the antisense strand of the miR-203 locus, which plays a role in epithelial differentiation. Other differentially expressed miRNAs included hematopoietic-specific miRNAs such as miR-142-3p and miR-223/223, and angiogenic miRNAs such as miR-21, miR-378, miR-100 and miR-31, which was the most highly upregulated miRNA in psoriatic skin. The functions of these miRNAs are consistent with the inflammatory and hyperproliferative phenotype of psoriatic lesions. In situ hybridization of differentially expressed miRNAs revealed stratified epidermal expression of an uncharacterized keratinocyte-derived miRNA, miR-135b, as well as the epidermal infiltration of the hematopoietic-specific miRNA, miR-142-3p, in psoriatic lesions. This study lays a critical framework for functional characterization of miRNAs in healthy and diseased skin.
银屑病是一种慢性且复杂的炎症性皮肤疾病，其病变显示出明显改变的 mRNA 表达谱。然而，对于小 RNA 的表达却知之甚少。在这里，我们描述了在一个大的患者队列中使用下一代测序对正常和银屑病皮肤 miRNAome 的全面分析。我们生成了 6.7×10^8 个小 RNA 读数，代表 717 个已知和 284 个推测的新 microRNAs（miRNAs）。我们还观察到已知和新 miRNA 基因座的 isomiRs 和 miRNAs 的广泛表达，以及正常和银屑病皮肤中 miRNA 编辑的低频率。用 qRT-PCR 在皮肤和其他人体组织或细胞系中对选定的新 miRNA 的表达和加工进行了确认。在银屑病皮肤中，80 个已知和 18 个新 miRNA 的表达呈 2-42 倍差异。特别重要的是，miR-203 基因座反义链衍生的一种经过验证的新 miRNA 的 2.7 倍上调，该 miRNA 在上皮分化中发挥作用。其他差异表达的 miRNA 包括造血特异性 miRNA，如 miR-142-3p 和 miR-223/223，以及血管生成 miRNA，如 miR-21、miR-378、miR-100 和 miR-31，这是银屑病皮肤中上调最明显的 miRNA。这些 miRNA 的功能与银屑病病变的炎症和过度增殖表型一致。差异表达 miRNA 的原位杂交显示，一种未表征的角质形成细胞衍生 miRNA，miR-135b，以及造血特异性 miRNA，miR-142-3p，在银屑病病变中的表皮浸润呈分层表达。这项研究为健康和患病皮肤中 miRNA 的功能特征奠定了关键框架。
