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基于基因表达谱研究脊髓损伤即刻阶段的候选长链非编码 RNA 和信使 RNA。

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

机构信息

Department of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, PR China.

Department of Orthopaedics, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, PR China.

出版信息

Gene. 2018 Jun 30;661:119-125. doi: 10.1016/j.gene.2018.03.074. Epub 2018 Mar 23.

Abstract

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.

摘要

脊髓损伤 (SCI) 是一种严重的破坏性疾病,具有较高的死亡率和发病率。SCI 即刻相的早期病理变化可能在继发性损伤的发展中起主要作用。许多长链非编码 RNA (lncRNA) 的表达改变已被证明在中枢神经系统疾病中发挥着重要作用。然而,lncRNA 和信使 RNA (mRNA) 在 SCI 即刻相的作用尚不清楚。我们在 SCI 后 2h 时的大鼠模型中检查了 mRNA 和 lncRNA 的表达情况,使用微阵列分析鉴定了差异表达的 lncRNA (DE lncRNA) 和差异表达的 mRNA (DE mRNA)。与对照样本相比,SCI 即刻相的脊髓样本中鉴定出 772 个 DE lncRNA 和 992 个 DE mRNA。此外,GO 术语注释结果表明,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、中性粒细胞外渗、巨噬细胞分化、单核细胞趋化和细胞对白细胞介素 1 (IL-1) 的反应是主要显著富集的 GO 术语。KEGG 富集分析的结果表明,DEGs 富集在 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 个高程度的枢纽节点,可能是 SCI 即刻相的重要靶点。本研究为 lncRNA 和 mRNA 如何调节 SCI 即刻相的发病机制提供了新的见解。

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