A miRNA signature in leukocytes from sporadic amyotrophic lateral sclerosis
A miRNA signature in leukocytes from sporadic amyotrophic lateral sclerosis
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DOI：
10.1016/j.gene.2012.07.058
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发表时间：
2012-10-15
期刊：
影响因子：
3.5
通讯作者：
Cotrufo, Roberto
中科院分区：
文献类型：
--
作者：
De Felice, Bruna;Guida, Marco;Cotrufo, Roberto
肌萎缩侧索硬化症（Amyotrophic lateral sclerosis，ALS）是一种进行性的、严重致残的成人神经系统疾病。越来越多的证据表明，在大脑中以空间和时间控制的方式表达的各种miRNA在神经元发育中起关键作用。此外，microRNA的失调有助于一些精神疾病和神经退行性疾病。在这里，我们分析了911人类miRNAs的表达谱，白细胞，最容易获得的人类组织细胞，从8例患者患有散发性肌萎缩侧索硬化症（sALS）和12名健康对照。采用TaqMan实时定量聚合酶链反应技术对14名sALS患者和14名对照进行验证，发现8个miRNAs在sALS患者中表达显著上调或下调。在白细胞中检测到的miRNA谱的显著变化与主要在神经系统中表达的miRNA有关。其中一种miRNAs，miR-338- 3 p，先前已被证明在ALS大脑中失调。这项研究首次在sALS的早期阶段检测到特定的microRNAs疾病相关的变化。我们认为，在sALS患者外周血白细胞中发现的miRNAs谱可能与了解sALS的发病机制有关和/或可用作该疾病的生物标志物。(C)2012爱思唯尔有限公司版权所有。
Amyotrophic lateral sclerosis (ALS) is a progressive and seriously disabling adult-onset neurological disease. Accumulating evidence indicates that various miRNAs, expressed in a spatially and temporally controlled manner in the brain, play a key role in neuronal development. In addition, misregulation of microRNAs contributes to some mental disorders and neurodegeneration diseases.Here, we analyzed the expression profiles of 911 human miRNAs using microarray technology in leukocytes, the most readily available human tissue cells, obtained from 8 patients affected by sporadic amyotrophic lateral sclerosis (sALS) and 12 healthy controls. An independent group of 14 sALS patients and 14 controls was used for validation by TaqMan real-time polymerase chain reaction assay.We identified 8 miRNAs that were significantly up- or downregulated in sALS patients as compared to healthy controls. The significant variations in miRNAs profiles detected in leukocytes have been related to miRNAs predominantly expressed in the nervous system. One of these miRNAs, miR-338-3p, has previously been shown to be de-regulated in ALS brains.This study, for the first time, detected specific microRNAs disease-related changes at an earlier stage of sALS. We suggest that miRNAs profiles found in the peripheral blood leukocytes from sALS patients can be relevant to understand the pathogenesis of sALS and/or used as biomarkers of the disease. (C) 2012 Elsevier B.V. All rights reserved.