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鉴定严重活动期斑秃患者血液 microRNA 的变化。

Identification of blood microRNA alterations in patients with severe active alopecia areata.

机构信息

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.

出版信息

J Cell Biochem. 2019 Sep;120(9):14421-14430. doi: 10.1002/jcb.28700. Epub 2019 Apr 15.

Abstract

BACKGROUND

Alopecia areata (AA) is a common inflammatory disease characterized by cellular infiltration of T cells targeting the anagen-stage hair follicle. Lack of efficacious treatment for AA may be due to little knowledge about its exact cellular mechanism. Studies have demonstrated that microRNAs (miRNAs) play an important role in the regulation of inflammatory skin diseases such as atopic dermatitis and psoriasis. However, little is known about the role of miRNAs in AA.

OBJECTIVE

The present study aimed to explore the blood miRNAs alterations in patients with severe active AA.

METHODS

We constructed a bipartite miRNA-messenger RNA (mRNA) regulatory network by the validated miRNA-mRNA relationships. Subsequently, the miRNA-miRNA synergistic network was formed in consideration of the Gene Ontology function enrichment of coregulated target genes. Lastly, the functional network was identified by the ingenuity pathway analysis.

RESULTS

By using an Agilent microarray that covers 2549 human miRNAs, we identified 36 significantly differentially expressed miRNAs in severe active AA patients. miRNA target gene prediction and functional annotation analysis showed significant enrichment in several pathways including the ribosome, cancer, cell cycle, insulin signaling, transforming growth factor-βsignaling, and p53 signaling pathways. Analysis of the three kinds of network showed that miR-185-5p, miR-125b-5p, and miR-186-5p might play important and synergistic roles in the active phase of AA. According to the receiver operating characteristic curve analysis, several miRNAs were selected for the quantitative real-time polymerase chain reaction validation. Among the miRNAs, miR-210 and miR-1246 had high prediction with high accuracy.

CONCLUSION

Blood dysregulated miRNAs are potentially associated with the severe active AA. These miRNAs could function synergistically and might be promising targets for the development of novel treatments for AA in the future.

摘要

背景

斑秃(AA)是一种常见的炎症性疾病,其特征是 T 细胞靶向生长期毛囊的细胞浸润。缺乏有效的 AA 治疗方法可能是由于对其确切的细胞机制知之甚少。研究表明,microRNAs(miRNAs)在特应性皮炎和银屑病等炎症性皮肤病的调节中发挥重要作用。然而,miRNAs 在 AA 中的作用知之甚少。

目的

本研究旨在探讨严重活动期 AA 患者血液中 miRNAs 的变化。

方法

我们通过验证的 miRNA-mRNA 关系构建了二分 miRNA-mRNA 调控网络。随后,考虑到共调控靶基因的基因本体功能富集,形成了 miRNA-miRNA 协同网络。最后,通过 Ingenuity 通路分析确定了功能网络。

结果

使用涵盖 2549 个人类 miRNAs 的 Agilent 微阵列,我们在严重活动期 AA 患者中鉴定出 36 个差异表达显著的 miRNAs。miRNA 靶基因预测和功能注释分析显示,几个通路包括核糖体、癌症、细胞周期、胰岛素信号转导、转化生长因子-β 信号转导和 p53 信号转导途径显著富集。三种网络的分析表明,miR-185-5p、miR-125b-5p 和 miR-186-5p 可能在 AA 的活动期发挥重要协同作用。根据受试者工作特征曲线分析,选择了几种 miRNA 进行定量实时聚合酶链反应验证。在这些 miRNAs 中,miR-210 和 miR-1246 具有高预测性和高精度。

结论

血液失调的 miRNAs 可能与严重活动期 AA 有关。这些 miRNAs 可能协同作用,并可能成为未来开发 AA 新型治疗方法的有前途的靶点。

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