中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (9): 1610-1616.doi: 10.4103/1673-5374.255998

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

整合生物信息学分析人脐带间充质干细胞移植治疗缺血性脑梗死相关的miRNA-mRNA调控网络

  

  • 出版日期:2019-09-15 发布日期:2019-09-15
  • 基金资助:

    国家重点研发计划项目（2016YFC1301600），吉林省科学技术创新项目（2017TD-12）

Identification of microRNAs and messenger RNAs involved in human umbilical cord mesenchymal stem cell treatment of ischemic cerebral infarction using integrated bioinformatics analysis

 Yin-Meng Qu 1 , Xin Sun 1 , Xiu-Li Yan 1 , Hang Jin 1 , Zhen-Ni Guo 2 , Yi Yang 1, 2   

  1. 1 Stroke Center, Neuroscience Center, Department of Neurology, the First Hospital of Jilin University, Changchun, Jilin Province, China
    2 Clinical Trial and Research Center for Stroke, Department of Neurology, the First Hospital of Jilin University, Changchun, Jilin Province, China
  • Online:2019-09-15 Published:2019-09-15
  • Contact: Yi Yang, PhD, MD, doctoryangyi@163.com; Zhen-Ni Guo, MD, zhen1ni2@163.com.
  • Supported by:

    This study was supported by the National Key Research & Development Program of China, No. 2016YFC1301600, and Program for Jilin University Science and Technology Innovation Team, No. 2017TD-12 (both to YY).

PDF

167

摘要：

近年来在人脐带间充质干细胞移植治疗缺血性脑梗死中发现了大量的差异表达基因，这些基因能参与多种生化过程，而miRNA在这一过程中的作用还存在疑问。为此，作者从Gene Expression Omnibus（GEO）数据库下载微阵列数据集GSE78731（mRNA谱）和GSE97532（miRNA谱），筛选人脐带间充质干细胞移植治疗大鼠与缺血性脑梗死大鼠差异表达的基因；随后在通过基因注释，DAVID网站和可视化的在线数据库进行基因本体论富集分析和途径富集分析；(1)应用鉴定的基因进行WGCNA分析以建立加权共表达网络模型；通过Cytoscape构建蛋白质-蛋白质相互作用网络，并且通过MCODE插件从蛋白质-蛋白质相互作用网络提取最高度相关的子网络；(2)由在线数据库starBase v3.0预测差异表达的miRNA的靶基因；(3)共鉴定出3698个差异表达基因，与人脐带间充质干细胞移植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。在人脐带间充质干细胞移植治疗治疗缺血性脑梗死大鼠后鉴定了12个差异表达miRNA，主要涉及调节中性粒细胞迁移等的炎症信号传导通路；(4)研究已经确定了一系列差异表达的miRNA-mRNA和缺血性脑梗死相关人脐带间充质干细胞移植治疗的信号通路。此项生物信息学分析将为人脐带间充质干细胞移植治疗缺血性脑梗死治疗提供新的线索。

orcid: 0000-0002-9729-8522 (Yi Yang)
          0000-0002-8922-3862 (Zhen-Ni Guo)

关键词: 缺血性脑梗死, 人脐带间充质干细胞移植治疗, 生物信息学, 差异表达mRNA, 炎症反应, 干细胞疗法, 加权基因共表达网络分析, 蛋白质-蛋白质相互作用网络

Abstract:

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 identi¬fied 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 fur¬ther research into hUMSC treatment of ischemic cerebral infarction.

Key words: nerve regeneration, ischemic cerebral infarction, human umbilical cord mesenchymal stem cell treatment, bioinformatics analysis, differentially expressed genes, differentially expressed mRNAs, inflammatory response, stem cell therapy, weighted gene co-suppression analysis, WGCNA, protein-protein interaction network, PPI, hUMSC, neural regeneration