Network Analysis Reveals TNF as a Major Hub of Reactive Inflammation Following Spinal Cord Injury

Zhu, Weiping; Chen, Xuning; Ning, Le; Jin, Kan

doi:10.1038/s41598-018-37357-1

Cited by 11 publications

(7 citation statements)

References 58 publications

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“…The turquoise module and brown module were imported into Cytoscape for topology analysis. The topological parameters of all nodes in the two module networks (Tables SVI and SVII) were calculated and the top 30 nodes of each module were screened (33), which were selected to draw the network diagram, as presented in Fig. 4B and C.…”

Section: Resultsmentioning

confidence: 99%

Identification of prognostic markers of lung cancer through bioinformatics analysis and in vitro experiments

et al. 2019

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Lung cancer is one of the most common types of cancer worldwide. Understanding the molecular mechanisms underlying the development and progression of lung cancer may improve early diagnosis, treatment and prognosis. The aim of the present study was to examine the pathogenesis of lung cancer and to identify potentially novel biomarkers. Gene expression datasets of patients with lung cancer were obtained from the Gene Expression Omnibus. Genes which were most closely associated with lung cancer (core genes) were screened by weighted gene co-expression network analysis. In vitro cell based experiments were further utilized to verify the effects of the core genes on the proliferation of lung cancer cells, adhesion between cells and the matrix, and the associated metabolic pathways. Based on WGCNA screening, two gene modules and five core genes closely associated with lung cancer, including immunoglobulin superfamily member 10 (IGSF10) from the turquoise module, and ribonucleotide reductase regulatory subunit M2, protein regulator of cytokinesis 1, kinesin family member (KIF)14 and KIF2C from the brown module were identified as relevant. Survival analysis and differential gene expression analysis showed that there were significant differences in IGSF10 expression levels between the healthy controls and patients with lung cancer. In patients with lung cancer, IGSF10 expression was decreased, and the overall survival time of patients with lung cancer was significantly shortened. An MTT and colony formation assay showed that IGSF10-knockout significantly increased proliferation of lung cancer cells, and Transwell assays and adhesion experiments further suggested that the adhesion between cells and the matrix was significantly increased in IGSF10-knockout cells. Gene Set Enrichment Analysis showed that the expression level of IGSF10 was significantly associated with the activation of the integrin-β1/focal adhesion kinase (FAK) pathway. Western blotting revealed that knockout of IGSF10 resulted in the activation of the integrin-β1/FAK pathway, as the protein expression levels of integrin-β1, phosphorylated (p)-FAK and p-AKT were significantly upregulated. Activation of the integrin-β1/FAK pathway, following knockout of IGSF10, affected the proliferation and adhesion of lung cancer cells. Therefore, IGSF10 my serve as a potential prognostic marker of lung cancer.

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Section: Resultsmentioning

confidence: 99%

Identification of prognostic markers of lung cancer through bioinformatics analysis and in vitro experiments

et al. 2019

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“…It is well known that TNF serves as a major hub of reactive inflammation following SCI. TNF is involved in cellular response, metabolic processes, protein and receptor binding, and TNF signaling pathways (27). In addition, previous reports have shown that up-regulation of downstream substrates of the TNF pathway will evoke apoptosis of injured spinal cord neurons (28)(29)(30).…”

Section: Discussionmentioning

confidence: 99%

Changes in transcriptome profiling during the acute/subacute phases of contusional spinal cord injury in rats

Gong¹,

Li³

et al. 2020

Ann Transl Med

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Background: Spinal cord injuries (SCIs), along with subsequent secondary injuries, often result in irreversible damage to both sensory and motor functions. However, a thorough view of the underlying pathological mechanisms of SCIs, especially in a temporal-spatial manner, is still lacking.Methods: To obtain a comprehensive, real-time view of multiple subsets of the cellular mechanisms involved in SCIs, we applied RNA-sequencing technology to characterize the temporal changes in gene expression around the lesion site of contusion SCI in rats. First, we identified the differentially expressed genes (DEGs) in contrast to sham controls at 1, 4, and 7 days post SCI. Through bioinformatics analysis, including Pathway analysis, Gene-act-net, and Pathway-act-net, we screened and verified potential key pathways and genes associated with either the acute or subacute stages of SCI pathology. Results:The top three overrepresented pathways were associated with cytokine-cytokine receptor interaction, TNF signaling pathway, and cell cycle at day 1; lysosome, cytokine-cytokine receptor interaction, phagosome at day 4; and phagosome, lysosome, cytokine-cytokine receptor interaction at day 7 post injury.Further, we identified uniquely enriched genes at each time point, such as Ccr1 and Nos2 at day 1; as well as Mgst2, and Pla2g3 at 4 and 7 days post-injury.Conclusions: Our pathway analysis suggested a transition from inflammatory responses to multiple forms of cell death processes from the acute to subacute stages of SCI. Further, our results revealed a continuous transformation from a more inflammatory to an apoptotic/self-repairing transcriptome following the timecourse of SCIs. Our research provides novel insights into the molecular mechanisms of SCI pathophysiology and identifies potential targets for therapeutic intervention after SCI.

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“…Based on this idea, multiple potential 'biomarkers' have been measured and identified as significantly changed in ASCI patients. Most of these 'biomarkers' are inflammatory factors, including pro-inflammatory cytokines, such as TNF and interleukins, which is expected since increased inflammation has been well-evident in the spinal cord within minutes of injury [25,26]. However, the sensitivity and specificity of these inflammatory factors are either not evaluated or not high enough to always accurately distinguish the severity of acute spinal cord injury.…”

Section: Discussionmentioning

confidence: 99%

Correlation between miRNA-124, miRNA-544a, and TNF-α levels in acute spinal cord injury

Chang

et al. 2022

Spinal Cord

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Study design Retrospective. Objectives Acute spinal cord injury (ASCI) is caused by direct or indirect strikes from external forces on the spinal cord. Here, we investigated the correlation between the miR-124, miR-544a, and TNF-α levels in patients with ASCI, aiming to evaluate the potential usage of miR-124 and miR-544a in ASCI diagnosis. Setting University/hospital. Methods A total of 90 (58 male/32 female) ASIA patients and 15 (9 male/6 female) control patients (with acute limb trauma) were involved in the presented study. The ASIA patients were further subclustered based on the International Standards for the Neurological Classification of SCI (ISNCSCI) exam. 30 (18 male/12 female)cases were determined to have complete spinal cord injury (CSCI) and classified as ASIA grade A (Complete); 30 (20 male/10 female) cases were determined to have incomplete spinal cord injury (ISCI) and classified as ASIA grade B (sensory incomplete), C (motor incomplete), or D (motor incomplete); 30 (20 male/10 female) cases were determined to have normal neurological function (NNF) and classified as ASIA grade E (Normal). Plasma miR-124, miRNA-544a, and tumor necrosis factor-alpha (TNF-α) levels were measured from the blood samples collected 24 h, 48 h, and 72 h after trauma. Results The levels of miR-124 and miR-544a in the CSCI and ISCI groups were significantly higher than those of the NNF and the control group 24 h after injury (P < 0.05). The increased levels gradually declined from 24 h to 72 h after injury. The area under the receiver operating characteristic curve (ROC) of miR-124, miR-544a and TNF-α 24 h after trauma in patients with acute spinal cord injury were 0.948 [95% CI (0.890, 1.000)], 0.815 [95% CI (0.638, 0.994)] and 0.770 [95% CI (0.641, 0.879)], respectively. Conclusion The miRNA-124 and miRNA-544a levels increased significantly in ASCI patients compared with control patients 24 h after injury. These increased levels gradually reduced from 24 h to 72 h after injury. There is a strong positive correlation between miRNA-124, miRNA-544a, and acute spinal cord injury. Sponsorship The present study was supported by a University-level project of Ningxia Medical University (Project Number: XY2017147).

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Network Analysis Reveals TNF as a Major Hub of Reactive Inflammation Following Spinal Cord Injury

Cited by 11 publications

References 58 publications

Identification of prognostic markers of lung cancer through bioinformatics analysis and in vitro experiments

Identification of prognostic markers of lung cancer through bioinformatics analysis and in vitro experiments

Changes in transcriptome profiling during the acute/subacute phases of contusional spinal cord injury in rats

Correlation between miRNA-124, miRNA-544a, and TNF-α levels in acute spinal cord injury

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