Investigation of candidate long noncoding RNAs and messenger RNAs in the immediate phase of spinal cord injury based on gene expression profiles

Investigation of candidate long noncoding RNAs and messenger RNAs in the immediate phase of spinal cord injury based on gene expression profiles
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基于基因表达谱研究脊髓损伤即时阶段的候选长非编码 RNA 和信使 RNA

DOI:
10.1016/j.gene.2018.03.074
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发表时间:
2018
期刊:
影响因子:
3.5
通讯作者:
Feng Shiqing
Feng Shiqing
中科院分区:
生物学3区
文献类型:
--
作者:
Zhou Hengxing;Shi Zhongju;Kang Yi;Wang Yao;Lu Lu;Pan Bin;Liu Jun;Li Xueying;Liu Lu;Wei Zhijian;Kong Xiaohong;Feng Shiqing

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脊髓损伤(SCI)是一种严重的破坏性疾病,具有很高的死亡率和发病率。脊髓损伤即时期的早期病理改变可能在继发性损伤的发生中起重要作用。许多长链非编码rna (lncRNAs)表达的改变已被证明在中枢神经系统疾病中起着重要作用。然而,lncrna和信使rna (mrna)在SCI即时期的作用尚不清楚。我们在脊髓损伤后2 h检测了大鼠模型中mrna和lncRNAs的表达,并使用微阵列分析鉴定了差异表达的lncRNAs (DE lncRNAs)和差异表达的mrna (DE mrna)。与对照样本相比,在脊髓损伤后的即时阶段,脊髓样本中鉴定出772个DE lncrna和992个DE mrna。此外,基因本体(Gene Ontology, GO)术语注释结果显示,CXCR趋化因子受体结合、中性粒细胞凋亡过程、中性粒细胞迁移、中性粒细胞外溢、巨噬细胞分化、单核细胞趋化和细胞对白细胞介素-1 (IL-1)的反应是显著富集的主要GO术语。京都基因与基因组百科全书(KEGG)富集分析结果显示,这些DEGs富集于toll样受体信号通路、p53信号通路、MAPK信号通路和Jak-STAT信号通路。IL6、MBOAT4、FOS、TNF、JUN、STAT3、CSF2、MYC、CCL2和FGF2是前10个高度枢纽节点,可能是SCI即时期的重要靶点。目前的研究为lncRNAs和mrna如何调控脊髓损伤后即刻期的发病机制提供了新的见解。
Spinal cord injury (SCI) is a serious devastating condition and it has a high mortality rate and morbidity rate. The early pathological changes in the immediate phase of SCI may play a major part in the development of secondary injury. Alterations in the expression of many long noncoding RNAs (lncRNAs) have been shown to play fundamental roles in the diseases of the central nervous system. However, the roles of lncRNAs and messenger RNAs (mRNAs) in the immediate phase of SCI are not clear. We examined the expression of mRNAs and lncRNAs in a rat model at 2 h after SCI and identified the differentially expressed lncRNAs (DE lncRNAs) and differentially expressed mRNAs (DE mRNAs) using microarray analysis. 772 DE lncRNAs and 992 DE mRNAs were identified in spinal cord samples in the immediate phase following SCI compared with control samples. Moreover, Gene Ontology (GO) term annotation results showed that CXCR chemokine receptor binding, neutrophil apoptotic process, neutrophil migration, neutrophil extravasation, macrophage differentiation, monocyte chemotaxis and cellular response to interleukin-1 (IL-1) were the main significantly enriched GO terms. The results of Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the DEGs were enriched in toll−like receptor signaling pathway, p53 signaling pathway, MAPK signaling pathway and Jak–STAT signaling pathway. IL6, MBOAT4, FOS, TNF, JUN, STAT3, CSF2, MYC, CCL2 and FGF2 were the top 10 high-degree hub nodes and may be important targets in the immediate phase of SCI. The current study on provides novel insights into how lncRNAs and mRNAs regulate the pathogenesis of the immediate phase after SCI.