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多发性硬化症患者血液中的差异 microRNA 表达。

Differential microRNA expression in blood in multiple sclerosis.

机构信息

Department of Neurology, Copenhagen University Hospital Rigshospitalet, Denmark.

出版信息

Mult Scler. 2013 Dec;19(14):1849-57. doi: 10.1177/1352458513490542. Epub 2013 Jun 17.

Abstract

BACKGROUND

microRNAs (miRNAs) regulate the expression of the genome at the post-transcriptional level. They play a role in autoimmunity and inflammation, and show potential for use as therapeutic targets in many diseases. With the recent detection of miRNAs in body fluids, the possibility for using miRNAs as diagnostic biomarkers has emerged.

OBJECTIVE

We assessed whether miRNAs contribute to the altered immune activation state in relapsing-remitting multiple sclerosis (RRMS) patients and investigated the possible use of miRNAs as diagnostic biomarkers in multiple sclerosis (MS).

METHODS

We performed global miRNA expression profiling analysis in peripheral blood mononuclear cells (PBMCs) and selected miRNAs were measured in plasma. We detected expression of miRNAs by real-time qPCR and compared results with cytokines related to inflammation and disease activity. Selected miRNAs were analyzed in PBMC subpopulations, after isolating them by magnetic bead separation.

RESULTS

We found that among validated miRNAs, let-7d correlated with the pro-inflammatory cytokine interleukin-1B. The miR-145 was 3-fold up-regulated in MS patients; its possible use as a diagnostic biomarker in PBMCs, plasma and serum was confirmed by ROC-curve analysis (Area under the curve (AUC) 0.785, p = 0.0004; 0.785, p = 0.004; 0.981, P < 0.0001, respectively).

CONCLUSIONS

RRMS patients in remission had altered expression of miRNAs. We validated miR-145 as a potential diagnostic biomarker for the diagnosis of MS in blood, plasma and serum.

摘要

背景

microRNAs(miRNAs)在后转录水平上调节基因组的表达。它们在自身免疫和炎症中发挥作用,并在许多疾病中显示出作为治疗靶点的潜力。随着最近在体液中检测到 miRNAs,它们作为诊断生物标志物的可能性已经出现。

目的

我们评估了 miRNAs 是否导致复发缓解型多发性硬化症(RRMS)患者免疫激活状态的改变,并研究了 miRNAs 作为多发性硬化症(MS)诊断生物标志物的可能用途。

方法

我们对外周血单核细胞(PBMCs)进行了全局 miRNA 表达谱分析,并在血浆中测量了选定的 miRNA。我们通过实时 qPCR 检测 miRNA 的表达,并将结果与与炎症和疾病活动相关的细胞因子进行比较。通过磁珠分离分离 PBMC 亚群后,分析选定的 miRNA。

结果

我们发现,在验证的 miRNAs 中,let-7d 与促炎细胞因子白细胞介素-1B 相关。miR-145 在 MS 患者中上调了 3 倍;通过 ROC 曲线分析(曲线下面积(AUC)为 0.785,p = 0.0004;0.785,p = 0.004;0.981,P < 0.0001),证实了其在 PBMCs、血浆和血清中作为诊断生物标志物的可能用途。

结论

缓解期 RRMS 患者的 miRNA 表达发生改变。我们验证了 miR-145 作为血液、血浆和血清中 MS 诊断的潜在诊断生物标志物。

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