脊髓损伤分子机制的生物信息学分析-东南大学学报医学版

脊髓损伤分子机制的生物信息学分析

作者：刘冬

单位：东南大学附属中大医院, 江苏南京 210009

分类号：R651.2;Q811.4

出版年·卷·期（页码）：2021·40·第一期（89-96）

摘要：

目的：探讨创伤性脊髓损伤（spinal cord injury，SCI）的分子机制。方法：从GEO数据库下载SCI组和假手术组GSE45006基因芯片数据，通过GEO2R在线工具筛选差异表达基因（DEG）。使用DAVID和WebGestalt数据库进行DEG的功能富集分析。从STRING数据库构建蛋白质-蛋白质相互作用（PPI）网络，并通过软件Cytoscape及其MCODE插件模块分析，再利用DAVID数据库重新分析。结果：与假手术相比，在创伤后的1、3 d和1、2、8周分别鉴定出2 155、885、1 278、1 006、1 003个DEGs。在创伤后的1、3 d和1周，对其生物信息学分析发现，DEGs富集于炎症反应和免疫反应。通过PPI网络构建及模块分析发现20个中心节点，20个基因经DAVID数据库重新KEGG分析后发现CCNA2、Cdk1、Mcm2、Mcm4、Mcm6基因显著富集于细胞周期途径，可能在SCI发生发展中起到关键作用。结论：本研究提供了有关创伤性SCI分子机制的见解，可能有益于未来SCI研究并有助于治疗的发展。

Objective: To explore the molecular mechanisms of traumatic spinal cord injury (SCI). Methods: The GSE45006 gene expression profile was obtained from the Gene Expression Omnibus Database, and differentially expressed genes (DEG) were screened by the GEO2R tool online. Functional enrichment analysis of DEG was performed using DAVID and WebGestalt databases. A protein-protein interaction network was constructed from the STRING database, analyzed by Cytoscape and its MCODE plug-in module, and reanalyzed by the DAVID database. Results: Compared with sham surgery group, 2155, 885, 1278, 1006, and 1003 DEGs were identified 1 day, 3 days, 1 week, 2 weeks, and 8 weeks after trauma, respectively. Bioinformatics analysis on day 1, 3, and 1 week after-trauma found that DEGs were enriched in inflammatory and immune responses. Through the PPI network construction and module analysis, 20 central nodes were found. After 20 genes were re-KEGG analyzed by DAVID database, CCNA2, Cdk1, Mcm2, Mcm4, and Mcm6 genes were significantly enriched in the cell cycle pathway, which may play a key role in the development of spinal cord injury.Conclusion: This study provides insights into the molecular mechanisms of SCI, which may be beneficial for future SCI research and contribute to the development of treatment.

参考文献：

[1] ACKERY A,TATOR C,KRASSIOUKOV A.A global perspective on spinal cord injury epidemiology[J].J Neurotrauma,2004,21(10):1355-1370
[2] AHUJA C S,WILSON J R,NORI S,et al.Traumatic spinal cord injury[J].Neurosurgery,2017,80(3S):S9-S22.
[3] KIM Y H,HA K Y,KIM S I.Spinal cord injury and related clinical trials[J].Clin Orthop Surg,2017,9(1):1-9.
[4] SIDDIQUI A M,KHAZAEI M,FEHLINGS M G.Translating mechanisms of neuroprotection,regeneration,and repair to treatment of spinal cord injury[J].Prog Brain Res,2015,218:15-54.
[5] TATOR C H,FEHLINGS M G.Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms[J].J Neurosurg,1991,75(1):15-26.
[6] FEHLINGS M G,PERRIN R G.The timing of surgical intervention in the treatment of spinal cord injury:a systematic review of recent clinical evidence[J].Spine,2006,31(Supplement):S28-S35.
[7] BAREYRE F M,SCHWAB M E.Inflammation,degeneration and regeneration in the injured spinal cord:insights from DNA microarrays[J].Trends Neurosci,2003,26(10):555-563.
[8] YDENS E,PALMERS I,HENDRIXS,et al.The next generation of biomarker research in spinal cord injury[J].Mol Neurobiol,2017,54(2):1482-1499.
[9] CHEN G,FANG X,YU M.Regulation of gene expression in rats with spinal cord injury based on microarray data[J].Mol Med Rep,2015,12(2):2465-2472.
[10] ZHU Z,SHEN Q,ZHU L,et al.Identification of pivotal genes and pathways for spinal cord injury via bioinformatics analysis[J].Mol Med Rep,2017,16(4):3929-3937.
[11] ZHAO S,ZHOU W,CHEN J,et al.Bioinformatics analysis of the molecular mechanisms underlying traumatic spinal cord injury[J].Mol Med Rep,2018,17(6):8484-8492.
[12] DAVIS S,MELTZER P S.GEOquery:a bridge between the Gene Expression Omnibus (GEO) and BioConductor[J].Bioinformatics,2007,23(14):1846-1847.
[13] HUANG D W,SHERMAN B T,LEMPICKI R A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources[J].Nat Protoc,2009,4(1):44-57.
[14] WANG J,DUNCAN D,SHI Z,et al.WEB-based GEne SeT AnaLysis Toolkit (WebGestalt):update 2013[J].Nucleic Acids Res,2013,41(Web Server issue):W77-83.
[15] SZKLARCZYK D,FRANCESCHINI A,WYDER S,et al.STRING v10:protein-protein interaction networks,integrated over the tree of life[J].Nucleic Acids Res,2015,43(Database issue):D447-452.
[16] SHANNON P,MARKIEL A,OZIER O,et al.Cytoscape:a software environment for integrated models of biomolecular interaction networks[J].Genome Res,2003,13(11):2498-2504.
[17] KJELL J,OLSON L.Rat models of spinal cord injury:from pathology to potential therapies[J].Dis Model Mech,2016,9(10):1125-1137.
[18] SAGHAZADEH A,REZAEI N.The role of timing in the treatment of spinal cord injury[J].Biomed Pharmacother,2017,92:128-139.
[19] KINOSHITA T,NAKAMURA T,UMEMOTO Y,et al.Increase in interleukin-6 immediately after wheelchair basketball games in persons with spinal cord injury:preliminary report[J].Spinal Cord,2013,51(6):508-510.
[20] JIN W,WANG J,ZHU T,et al.Anti-inflammatory effects of curcumin in experimental spinal cord injury in rats[J].Inflamm Res,2014,63(5):381-387.
[21] HU J Z,HUANG J H,XIAO Z M,et al.Tetramethylpyrazine accelerates the function recovery of traumatic spinal cord in rat model by attenuating inflammation[J].J Neurol Sci,2013,324(1-2):94-99.
[22] KRASNOV G S,PUZANOV G A,KUDRYAVTSEVA A V,et al.[Differential expression of an ensemble of the key genes involved in cell-cycle regulation in lung cancer[J].Mol Biol (Mosk),2017,51(5):849-856.
[23] SHI Z,NING G,ZHANG B,et al.Signatures of altered long noncoding RNAs and messenger RNAs expression in the early acute phase of spinal cord injury[J].J Cell Physiol,2019,234(6):8918-8927.
[24] WU J,ZHAO Z,SABIRZHANOV B,et al.Spinal cord injury causes brain inflammation associated with cognitive and affective changes:role of cell cycle pathways[J].J Neurosci,2014,34(33):10989-11006.
[25] WU J,KHAREBAVA G,PIAO C,et al.Inhibition of E2F1/CDK1 pathway attenuates neuronal apoptosis in vitro and confers neuroprotection after spinal cord injury in vivo[J].PLoS One,2012,7(7):e42129.
[26] BAILIS J M,FORSBURG S L.MCM proteins:DNA damage,mutagenesis and repair[J].Curr Opin Genet Dev,2004,14(1):17-21.
[27] FORSBURG S L.Eukaryotic MCM proteins:beyond replication initiation[J].Microbiol Mol Biol Rev,2004,68(1):109-131.
[28] CHEN G,FANG X,YU M.Regulation of gene expression in rats with spinal cord injury based on microarray data[J].Mol Med Rep,2015,12(2):2465-2472.

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