Yang Qinghe, Pan Wei, Qian Liwei
a Department of Neurology , The Second People's Hospital of Liaocheng , Shandong , China.
b Department of Pediatric , The Second People's Hospital of Liaocheng , Shandong , China.
Neurol Res. 2017 Feb;39(2):142-151. doi: 10.1080/01616412.2016.1250857. Epub 2016 Nov 4.
Multiple sclerosis (MS) is the common neurological disorders in young adults, which affects the central nervous system myelin or oligodendrocytes and results in disability. This study aimed to identify the key miRNAs in blood of patients in MS for better understanding the underlying mechanisms of MS.
The publicly available Gene Expression Omnibus data-sets of MS were performed to integrated analysis. miRNA expression and mRNA expression were analyzed in whole blood samples from patients with MS and healthy controls by microarray analysis, Gene Ontology enrichment analyses, Kyoto Encyclopedia of Genes and Genomes pathway analyses, construction of miRNA-mRNA interaction network, and quantitative real-time polymerase reaction.
In patients with MS, microarray analysis identified 45 significantly dysregulated miRNAs and 621 significantly dysregulated mRNAs. 1165 negative correlation pairs of miRNA-mRNA were predicted and used to construct the interaction network. hsa-miR-30a, hsa-miR-93, hsa-miR-20b, and hsa-miR-20a occurred as central hubs regulating 87, 38, 34, and 34 genes. Dysregulated mRNAs were significantly enriched in ribosome, tuberculosis, and pathways in cancer. The verification of qRT-PCR displayed that hsa-miR-328-3p was significantly up-regulated in MS and its target genes RAC2 had the down-regulated tendency in MS. hsa-miR-20a-5p had the up-regulated tendency and the corresponding target gene EIF4EBP2 had the down-regulated tendency in MS compared to healthy controls.
hsa-miR-30a, hsa-miR-93, hsa-miR-20b, and hsa-miR-20a might be the key participant in the pathophysiology of MS involved in signaling pathways including ribosome, tuberculosis, and pathways in cancer.
多发性硬化症（MS）是年轻成年人中常见的神经系统疾病，它会影响中枢神经系统的髓磷脂或少突胶质细胞并导致残疾。本研究旨在确定MS患者血液中的关键微小RNA（miRNA），以便更好地理解MS的潜在机制。
对公开可用的MS基因表达综合数据库进行整合分析。通过微阵列分析、基因本体富集分析、京都基因与基因组百科全书通路分析、构建miRNA-信使核糖核酸（mRNA）相互作用网络以及定量实时聚合酶反应，分析MS患者和健康对照者全血样本中的miRNA表达和mRNA表达。
在MS患者中，微阵列分析鉴定出45个显著失调的miRNA和621个显著失调的mRNA。预测了1165对miRNA-mRNA负相关对并用于构建相互作用网络。hsa-miR-30a、hsa-miR-93、hsa-miR-20b和hsa-miR-20a作为调控87、38、34和34个基因的中心枢纽出现。失调的mRNA在核糖体、结核病和癌症相关通路中显著富集。定量逆转录-聚合酶链反应（qRT-PCR）验证显示，hsa-miR-328-3p在MS中显著上调，其靶基因RAC2在MS中有下调趋势。与健康对照相比，hsa-miR-20a-5p在MS中有上调趋势，相应的靶基因EIF4EBP2在MS中有下调趋势。
hsa-miR-30a、hsa-miR-93、hsa-miR-20b和hsa-miR-20a可能是MS病理生理学的关键参与者，参与包括核糖体、结核病和癌症相关通路在内的信号通路。
