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多发性硬化症患者外周血单个核细胞中长链非编码RNA的表达谱

Expression Profile of Long Noncoding RNAs in Peripheral Blood Mononuclear Cells from Multiple Sclerosis Patients.

作者信息

Zhang Fang, Gao Chao, Ma Xiao-Feng, Peng Xiao-Lin, Zhang Rong-Xin, Kong De-Xin, Simard Alain R, Hao Jun-Wei

机构信息

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, China.

出版信息

CNS Neurosci Ther. 2016 Apr;22(4):298-305. doi: 10.1111/cns.12498. Epub 2016 Feb 4.

Abstract

AIMS

Long noncoding RNAs (lncRNAs) play a key role in regulating immunological functions. Their impact on the chronic inflammatory disease multiple sclerosis (MS), however, remains unknown. We investigated the expression of lncRNAs in peripheral blood mononuclear cells (PBMCs) of patients with MS and attempt to explain their possible role in the process of MS.

METHODS

For this study, we recruited 26 patients with MS according to the revised McDonald criteria. Then, we randomly chose 6 patients for microarray analysis. Microarray assays identified outstanding differences in lncRNA expression, which were verified through real-time PCR. LncRNA functions were annotated for target genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and regulatory relationships between lncRNAs and target genes were analyzed using the "cis" and "trans" model.

RESULTS

There were 2353 upregulated lncRNAs, 389 downregulated lncRNAs, 1037 upregulated mRNAs, and 279 downregulated mRNAs in patients with MS compared to healthy control subjects (fold change >2.0). Real-time PCR results of six aberrant lncRNAs were consistent with the microarray data. The coexpression network comprised 864 lncRNAs and 628 mRNAs. Among differentially expressed lncRNAs, 10 lncRNAs were predicted to have 10 cis-regulated target genes, and 33 lncRNAs might regulate their trans target genes.

CONCLUSIONS

We identified a subset of dysregulated lncRNAs and mRNAs. The differentially expressed lncRNAs may be important in the process of MS. However, the specific molecular mechanisms and biological functions of these lncRNAs in the pathogenesis of MS need further study.

摘要

目的

长链非编码RNA(lncRNA)在调节免疫功能中起关键作用。然而,它们对慢性炎症性疾病多发性硬化症(MS)的影响尚不清楚。我们研究了MS患者外周血单个核细胞(PBMC)中lncRNA的表达,并试图解释它们在MS发病过程中的可能作用。

方法

在本研究中,我们根据修订的麦克唐纳标准招募了26例MS患者。然后,我们随机选择6例患者进行微阵列分析。微阵列分析确定了lncRNA表达的显著差异,并通过实时PCR进行了验证。使用基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析对lncRNA的功能进行靶基因注释,并使用“顺式”和“反式”模型分析lncRNA与靶基因之间的调控关系。

结果

与健康对照受试者相比,MS患者中有2353个lncRNA上调,389个lncRNA下调,1037个mRNA上调,279个mRNA下调(倍数变化>2.0)。6个异常lncRNA的实时PCR结果与微阵列数据一致。共表达网络由864个lncRNA和628个mRNA组成。在差异表达的lncRNA中,预测有10个lncRNA具有10个顺式调控靶基因,33个lncRNA可能调控其反式靶基因。

结论

我们鉴定出了一组失调的lncRNA和mRNA。差异表达的lncRNA可能在MS发病过程中起重要作用。然而,这些lncRNA在MS发病机制中的具体分子机制和生物学功能需要进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d043/6492795/c00b23c63351/CNS-22-298-g001.jpg

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