Qu Yin-Meng, Sun Xin, Yan Xiu-Li, Jin Hang, Guo Zhen-Ni, Yang Yi
Stroke Center, Neuroscience Center, Department of Neurology, the First Hospital of Jilin University, Changchun, Jilin Province, China.
Clinical Trial and Research Center for Stroke, Department of Neurology, the First Hospital of Jilin University, Changchun, Jilin Province, China.
Neural Regen Res. 2019 Sep;14(9):1610-1616. doi: 10.4103/1673-5374.255998.
In recent years, a large number of differentially expressed genes have been identified in human umbilical cord mesenchymal stem cell (hUMSC) transplants for the treatment of ischemic cerebral infarction. These genes are involved in various biochemical processes, but the role of microRNAs (miRNAs) in this process is still unclear. From the Gene Expression Omnibus (GEO) database, we downloaded two microarray datasets for GSE78731 (messenger RNA (mRNA) profile) and GSE97532 (miRNA profile). The differentially expressed genes screened were compared between the hUMSC group and the middle cerebral artery occlusion group. Gene ontology enrichment and pathway enrichment analyses were subsequently conducted using the online Database for Annotation, Visualization, and Integrated Discovery. Identified genes were applied to perform weighted gene co-suppression analyses, to establish a weighted co-expression network model. Furthermore, the protein-protein interaction network for differentially expressed genes from turquoise modules was built using Cytoscape (version 3.40) and the most highly correlated subnetwork was extracted from the protein-protein interaction network using the MCODE plugin. The predicted target genes for differentially expressed miRNAs were also identified using the online database starBase v3.0. A total of 3698 differentially expressed genes were identified. Gene ontology analysis demonstrated that differentially expressed genes that are related to hUMSC treatment of ischemic cerebral infarction are involved in endocytosis and inflammatory responses. We identified 12 differentially expressed miRNAs in middle cerebral artery occlusion rats after hUMSC treatment, and these differentially expressed miRNAs were mainly involved in signaling in inflammatory pathways, such as in the regulation of neutrophil migration. In conclusion, we have identified a number of differentially expressed genes and differentially expressed mRNAs, miRNA-mRNAs, and signaling pathways involved in the hUMSC treatment of ischemic cerebral infarction. Bioinformatics and interaction analyses can provide novel clues for further research into hUMSC treatment of ischemic cerebral infarction.
近年来，在用于治疗缺血性脑梗死的人脐带间充质干细胞（hUMSC）移植中已鉴定出大量差异表达基因。这些基因参与各种生化过程，但微小RNA（miRNA）在此过程中的作用仍不清楚。我们从基因表达综合数据库（GEO）下载了两个微阵列数据集，分别为GSE78731（信使核糖核酸（mRNA）谱）和GSE97532（miRNA谱）。将筛选出的差异表达基因在hUMSC组和大脑中动脉闭塞组之间进行比较。随后使用在线注释、可视化和综合发现数据库进行基因本体富集和通路富集分析。将鉴定出的基因用于进行加权基因共抑制分析，以建立加权共表达网络模型。此外，使用Cytoscape（3.40版）构建来自绿松石模块的差异表达基因的蛋白质-蛋白质相互作用网络，并使用MCODE插件从蛋白质-蛋白质相互作用网络中提取相关性最高的子网。还使用在线数据库starBase v3.0鉴定差异表达miRNA的预测靶基因。共鉴定出3698个差异表达基因。基因本体分析表明，与hUMSC治疗缺血性脑梗死相关的差异表达基因参与内吞作用和炎症反应。我们在hUMSC治疗后的大脑中动脉闭塞大鼠中鉴定出12个差异表达的miRNA，这些差异表达的miRNA主要参与炎症通路中的信号传导，如中性粒细胞迁移的调节。总之，我们已经鉴定出一些参与hUMSC治疗缺血性脑梗死的差异表达基因、差异表达的mRNA、miRNA-mRNA和信号通路。生物信息学和相互作用分析可为进一步研究hUMSC治疗缺血性脑梗死提供新线索。
