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构建 lncRNA-miRNA-mRNA 网络以确定多发性硬化症中 Th1/Th2 失衡的关键调节因子。

Construction of a lncRNA-miRNA-mRNA network to determine the key regulators of the Th1/Th2 imbalance in multiple sclerosis.

机构信息

Department of Medical Genetics, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, 79196-93116, Iran.

Hormozgan University of Medical Sciences Research Center for Molecular Medicine, Bandar Abbas, 79196-93116, Iran.

出版信息

Epigenomics. 2021 Nov;13(22):1797-1815. doi: 10.2217/epi-2021-0296. Epub 2021 Nov 2.

Abstract

The exact epigenetic mechanisms that determine the balance of T helper (Th)1 and Th2 cells and autoimmune responses in multiple sclerosis (MS) remain unclear. We aim to clarify these. A combination of bioinformatics analysis and molecular evaluations was utilized to identify master hub genes. A competitive endogenous RNA network containing six long noncoding RNAs (lncRNAs), 21 miRNAs and 86 mRNAs was provided through enrichment analysis and a protein-protein interaction network. and were found as differentially expressed lncRNAs using Gene Expression Omnibus (GSE21942). Quantitative real-time PCR results demonstrate dysregulation in the (a regulator of Th1/Th2 balance),  and , as well as miR-544a and miR-210-3p (which directly target ). ELISA also confirmed an imbalance in IFN-γ (Th1)/IL-4 (Th2) in MS patients. Our findings introduce novel biomarkers leading to Th1/Th2 imbalance in MS.

摘要

确切的表观遗传机制决定了多发性硬化症(MS)中辅助性 T 细胞(Th)1 和 Th2 细胞以及自身免疫反应的平衡仍不清楚。我们旨在阐明这些机制。我们采用生物信息学分析和分子评估相结合的方法来鉴定主要的枢纽基因。通过富集分析和蛋白质-蛋白质相互作用网络,提供了包含六个长非编码 RNA(lncRNA)、21 个 miRNA 和 86 个 mRNA 的竞争内源性 RNA 网络。使用基因表达综合数据库(GSE21942)发现 (Th1/Th2 平衡的调节剂)和 是差异表达的 lncRNA。实时定量 PCR 结果表明,MS 患者中 (直接靶向 )和 miR-544a 和 miR-210-3p 的失调。ELISA 也证实了 MS 患者 IFN-γ(Th1)/IL-4(Th2)的失衡。我们的研究结果为 MS 中 Th1/Th2 失衡提供了新的生物标志物。

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