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过敏性皮炎复发模型中 lncRNAs、miRNAs 和 mRNA 相关 ceRNA 网络的综合分析。

Integrative Analysis of lncRNAs, miRNAs, and mRNA-Associated ceRNA Network in an Atopic Dermatitis Recurrence Model.

机构信息

Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.

出版信息

Int J Mol Sci. 2018 Oct 20;19(10):3263. doi: 10.3390/ijms19103263.

Abstract

Atopic dermatitis (AD) is a prevalent inflammatory skin disease characterized by its chronic nature and relapse. Ample evidence suggests that non-coding RNAs play a major role in AD pathogenesis. However, the mechanism remains unknown, particularly in AD recurrence. Dynamic morphological and cytokine changes were measured throughout the whole course of an FITC-induced AD recurrence murine model. Microarray assay and integrative analysis were performed to comprehensively explore long non-coding RNA (lncRNA), messenger RNA (mRNA), and microRNA (miRNA) networks. Our results showed that an AD recurrence model was established. Overall, 5766 lncRNAs, 4025 mRNAs, and 202 miRNAs changed after elicitation, whereas, 419 lncRNAs, 349 mRNAs, and more notably, only 23 miRNAs, were dysregulated in the remission phase. Gene ontology (GO) and KEGG pathway enrichment analyses were used to investigate the potential functions of the dysregulated genes. The altered regulation of seven miRNAs and seven lncRNAs were validated in different stages of the model. The competing endogenous RNA (ceRNA) network inferred that lncRNA humanlincRNA0490+ could compete for miR-155-5p binding, through which it might affect Pkiα expression. Altogether, our findings have provided a novel perspective on the potential roles of non-coding RNAs in AD, and suggest that specific non-coding RNAs could be new therapeutic targets against AD recurrence.

摘要

特应性皮炎(AD)是一种常见的炎症性皮肤病,其特征为慢性和复发。大量证据表明,非编码 RNA 在 AD 的发病机制中起主要作用。然而,其机制尚不清楚,尤其是在 AD 的复发中。在 FITC 诱导的 AD 复发小鼠模型的整个过程中,测量了动态形态和细胞因子变化。进行了微阵列分析和综合分析,以全面探索长非编码 RNA(lncRNA)、信使 RNA(mRNA)和 microRNA(miRNA)网络。我们的结果表明建立了 AD 复发模型。总体而言,在激发后有 5766 个 lncRNA、4025 个 mRNA 和 202 个 miRNA 发生改变,而在缓解阶段仅调节 419 个 lncRNA、349 个 mRNA,更重要的是,只有 23 个 miRNA 发生失调。基因本体论(GO)和 KEGG 通路富集分析用于研究失调基因的潜在功能。在模型的不同阶段验证了七个 miRNA 和七个 lncRNA 的改变调节。竞争内源性 RNA(ceRNA)网络推断,lncRNA humanlincRNA0490+ 可以与 miR-155-5p 竞争结合,通过这种方式它可能影响 Pkiα 的表达。总之,我们的研究结果为非编码 RNA 在 AD 中的潜在作用提供了新的视角,并表明特定的非编码 RNA 可能成为治疗 AD 复发的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/709a/6214145/b223b9a367ec/ijms-19-03263-g001.jpg

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