Institute for Systems Biology, Jianghan University, Wuhan 430056, China.
Department of Computer Science and Engineering, Washington University, Saint Louis, MO 63130, USA.
Int J Mol Sci. 2021 May 13;22(10):5182. doi: 10.3390/ijms22105182.
(1) Background: Understanding the function of circular RNAs (circRNAs), a class of noncoding RNA, in psoriatic skin can provide important insights into the complex regulation of genes contributing to the pathogenesis of psoriasis. (2) Methods: A novel method was applied to RNA-seq datasets from 93 skin biopsy samples to comprehensively identify circRNAs of all types, i.e., canonical circRNAs from the intron-exon junctions of mRNAs and interior circRNAs (i-circRNAs) from the interior regions of exons, introns, and intergenic regions. Selected circRNAs were experimentally validated by qRT-PCR and Sanger sequencing. CircRNAs with abundant and differential expression were identified and their putative function as competing endogenous RNAs (ceRNAs) was analyzed by an integrated analysis of circRNAs, microRNAs, and mRNAs. (3) Results: With a comprehensive search using no information of splicing signals, we systematically identified 179 highly abundant circRNAs in psoriatic skin. Many of these were reported for the first time and many were differentially expressed in involved versus normal or uninvolved skin. Validation based on three additional RNA-seq datasets confirmed most of the identified circRNAs in psoriatic skin. Experimental analyses confirmed the expression of the well-known circRNA CDR1as, a canonical circRNA, and a novel i-circRNA in psoriasis. We also identified many circRNAs that may act as ceRNAs to regulate the expression of mRNA genes in psoriasis-related signaling pathways in psoriasis. (4) Conclusions: The result of the study suggested that circRNAs are abundant in psoriatic skin, have distinct characteristics, and contribute to psoriatic pathogenesis.
(1) 背景：了解环状 RNA（circRNA），一种非编码 RNA 家族，在银屑病皮肤中的功能可以为基因的复杂调控提供重要的见解，这些基因有助于银屑病的发病机制。(2) 方法：应用一种新方法对来自 93 个皮肤活检样本的 RNA-seq 数据集进行分析，全面鉴定所有类型的 circRNA，即来自 mRNA 内含子-外显子连接处的经典 circRNA 和来自外显子、内含子和基因间区内部的内部 circRNA（i-circRNA）。通过 qRT-PCR 和 Sanger 测序对选定的 circRNA 进行实验验证。鉴定具有丰富和差异表达的 circRNA，并通过 circRNA、microRNA 和 mRNA 的综合分析分析其作为竞争性内源 RNA（ceRNA）的潜在功能。(3) 结果：使用不依赖剪接信号的全面搜索，我们系统地鉴定了银屑病皮肤中 179 个高度丰富的 circRNA。其中许多是首次报道的，许多在受累皮肤与正常或未受累皮肤之间存在差异表达。基于另外三个 RNA-seq 数据集的验证证实了银屑病皮肤中大多数鉴定的 circRNA。实验分析证实了 CDR1as，一种经典 circRNA 和一种新的 i-circRNA 在银屑病中的表达。我们还鉴定了许多 circRNA，它们可能作为 ceRNA 来调节银屑病相关信号通路中 mRNA 基因的表达。(4) 结论：该研究结果表明，circRNA 在银屑病皮肤中丰富存在，具有独特的特征，并有助于银屑病的发病机制。
