Jin Lingjing, Wu Zhourui, Xu Wei, Hu Xiao, Zhang Jin, Xue Zhigang, Cheng Liming
Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
Mol Biol Rep. 2014 May;41(5):3169-77. doi: 10.1007/s11033-014-3176-8. Epub 2014 Mar 5.
Spinal cord injury (SCI) leads to the loss of sensory, motor, and autonomic function. We aimed to identify the therapeutic targets of-SCI by bioinformatics analysis. The gene expression profile of GSE20907 was downloaded from gene expression omnibus database. By comparing gene expression profiles with control samples, we screened out several differentially expressed genes (DEGs) in 3 days, 2 weeks and 1 month post-SCI. The pathway enrichment and protein-protein interaction (PPI) network analysis for the identified DEGs were performed. Then, transcription factors and microRNAs for DEGs were predicted. We found that up-regulated DEGs mainly participated in cell cycle, oxidative phosphorylation and immune-related pathways; while down-regulated DEGs were mainly involved in oxidative phosphorylation and central nervous system disease signaling pathways. In the constructed PPI network, Bub1, Vascular endothelial growth factor, Topoisomerase IIα (TOP2a) and Cdc20 showed better correspondence with cell cycle, repair system and nerve system. Furthermore, the up-regulated genes (Arpc1b, CD74 and Brd2) significantly mapped to the target genes of transcription factors. The down-regulated genes of 3 days post-injury and the up-regulated genes of 2 weeks post-injury were significantly enriched as the target genes of microRNAs (miR-129 and miR-124). In conclusion, our results may provide guidelines to discuss the collaboration of PPI network in carcinogenesis of SCI.
脊髓损伤（SCI）会导致感觉、运动和自主神经功能丧失。我们旨在通过生物信息学分析确定SCI的治疗靶点。从基因表达综合数据库下载了GSE20907的基因表达谱。通过将基因表达谱与对照样本进行比较，我们筛选出了SCI后3天、2周和1个月时的几个差异表达基因（DEG）。对鉴定出的DEG进行了通路富集和蛋白质-蛋白质相互作用（PPI）网络分析。然后，预测了DEG的转录因子和微小RNA。我们发现上调的DEG主要参与细胞周期、氧化磷酸化和免疫相关通路；而下调的DEG主要涉及氧化磷酸化和中枢神经系统疾病信号通路。在构建的PPI网络中，Bub1、血管内皮生长因子、拓扑异构酶IIα（TOP2a）和Cdc20与细胞周期、修复系统和神经系统表现出更好的对应关系。此外，上调基因（Arpc1b、CD74和Brd2）显著映射到转录因子的靶基因。损伤后3天的下调基因和损伤后2周的上调基因作为微小RNA（miR-129和miR-124）的靶基因显著富集。总之，我们的结果可能为讨论PPI网络在SCI致癌过程中的协作提供指导。
