Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, 500 University Drive, MC-H171, Hershey, PA 17033-0850, USA.
Mol Biol Rep. 2012 May;39(5):6219-25. doi: 10.1007/s11033-011-1441-7. Epub 2012 Jan 10.
Multiple sclerosis (MS) is an immune-mediated, demyelinating and neurodegenerative disease of the central nervous system. After traumatic brain injury, it is the leading cause of neurology disability in young adults. Considerable advances have been made in identifying genes involved in MS but the genetic and phenotypic complexity associated with this disease significantly hinders any progress. A novel class of small RNA molecules, microRNAs (miRNAs) has acquired much attention because they regulate the expression of up to 30% of protein-coding genes and may play a pivotal role in the development of many, if not all, complex diseases. Seven published studies investigated miRNAs from peripheral blood mononuclear cells, CD4+, CD8+ T cell, B lymphocytes, peripheral blood leukocytes, whole blood and brain astrocytes with MS risk. The absence of MS studies investigating plasma miRNA prompted the current investigation of identifying a circulating miRNA signature in MS. We conducted a microarray analysis of over 900 known miRNA transcripts from plasma samples collected from four MS individuals and four sex-aged and ethnicity matched healthy controls. We identified six plasma miRNA (miR-614, miR-572, miR-648, miR-1826, miR-422a and miR-22) that were significantly up-regulated and one plasma miRNA (miR-1979) that was significantly down-regulated in MS individuals. Both miR-422a and miR-22 have previously been implicated in MS. The present study is the first to show a circulating miRNA signature involved in MS that could serve as a potential prognostic and diagnostic biomarker for MS.
多发性硬化症（MS）是一种中枢神经系统的免疫介导性、脱髓鞘和神经退行性疾病。在颅脑损伤后，它是导致年轻人神经系统残疾的主要原因。在确定与多发性硬化症相关的基因方面已经取得了相当大的进展，但与该疾病相关的遗传和表型复杂性严重阻碍了任何进展。一类新的小 RNA 分子，microRNAs（miRNAs）引起了广泛关注，因为它们可以调节多达 30%的蛋白质编码基因的表达，并且可能在许多（如果不是所有）复杂疾病的发生中发挥关键作用。有七项已发表的研究调查了来自外周血单核细胞、CD4+、CD8+T 细胞、B 淋巴细胞、外周血白细胞、全血和脑星形胶质细胞的 miRNAs 与多发性硬化症风险之间的关系。由于缺乏针对多发性硬化症患者血浆 miRNA 的研究，因此当前的研究旨在确定多发性硬化症患者的循环 miRNA 特征。我们对来自四个多发性硬化症患者和四个性别、年龄和种族匹配的健康对照者的血浆样本进行了超过 900 种已知 miRNA 转录物的微阵列分析。我们鉴定了六个在多发性硬化症患者中显著上调的血浆 miRNA（miR-614、miR-572、miR-648、miR-1826、miR-422a 和 miR-22）和一个显著下调的血浆 miRNA（miR-1979）。miR-422a 和 miR-22 先前均与多发性硬化症有关。本研究首次显示了与多发性硬化症相关的循环 miRNA 特征，可作为多发性硬化症的潜在预后和诊断生物标志物。
