Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Heilongjiang Province, Harbin, 150086, China.
Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Heilongjiang Province, Harbin, China.
J Mol Neurosci. 2022 Sep;72(9):1916-1928. doi: 10.1007/s12031-022-02007-9. Epub 2022 Jul 11.
Multiple sclerosis (MS) is a common chronic autoimmune disorder of the central nervous system that predominantly affects young adults. Mounting evidence indicates that deregulation of microRNAs (miRNAs) in cerebrospinal fluid (CSF) has been implicated in MS as a potential biomarker. However, comprehensive assessments of CSF miRNAs and their target genes are lacking. Here, aberrantly expressed CSF miRNAs of MS patients were obtained from numerous studies by manual search. With detailed information on these miRNAs, we utilized online databases to screen out immune-related target genes and further performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. To identify MS high-risk pathways and pivotal genes, pathway crosstalk and pathway-gene networks were constructed, followed by the establishment of a protein-protein interaction (PPI) network. The datasets collected from ArrayExpress were used to assess pivotal genes. Overall, 21 MS-related CSF miRNAs were included in this study. Subsequently, we identified 469 MS-related genes and 14 high-risk pathways. In the pathway-gene network, 27 critical MS-related genes participated in at least half of the high-risk pathways, and these genes were used to identify pivotal genes. Finally, miR-150, miR-328, and miR-34c-5p were determined to be risk miRNAs via the regulation of the pivotal risk genes MAPK1, AKT1, and VEGFA. Among them, VEGFA was validated to be significantly decreased in the CSF cells of MS patients by transcriptomic datasets. These findings may provide potential biomarkers or therapeutic targets and help elucidate the molecular mechanisms underlying the pathogenesis of MS.
多发性硬化症（MS）是一种常见的中枢神经系统慢性自身免疫性疾病，主要影响年轻人。越来越多的证据表明，脑脊液（CSF）中 microRNAs（miRNAs）的失调与 MS 有关，是一种潜在的生物标志物。然而，CSF miRNAs 及其靶基因的综合评估还很缺乏。在这里，我们通过手动搜索从众多研究中获得了 MS 患者的异常表达 CSF miRNAs。有了这些 miRNA 的详细信息，我们利用在线数据库筛选出免疫相关的靶基因，并进一步进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析。为了鉴定 MS 的高风险通路和关键基因，我们构建了通路串扰和通路-基因网络，并建立了蛋白质-蛋白质相互作用（PPI）网络。从 ArrayExpress 收集的数据集用于评估关键基因。总的来说，本研究纳入了 21 个与 MS 相关的 CSF miRNAs。随后，我们确定了 469 个与 MS 相关的基因和 14 个高风险通路。在通路-基因网络中，27 个关键 MS 相关基因参与了至少一半的高风险通路，这些基因被用于鉴定关键基因。最后，通过对关键风险基因 MAPK1、AKT1 和 VEGFA 的调控，确定了 miR-150、miR-328 和 miR-34c-5p 是风险 miRNAs。其中，VEGFA 通过转录组数据集被验证在 MS 患者的 CSF 细胞中显著减少。这些发现可能为提供潜在的生物标志物或治疗靶点，并有助于阐明 MS 发病机制的分子机制。
