Identification of potential biomarkers of gout through competitive endogenous RNA network analysis

Li, Yang; Huang, Caihuan; Yang, Zhenguo; Wang, Lei; Luo, Dan; Qi, Lü; Li, Zhichao; Huang, Yanqin

doi:10.1016/j.ejps.2022.106180

Cited by 10 publications

(8 citation statements)

References 45 publications

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“…BioGPS was an online tool that created as a centralized gene-annotation portal for clustering distributed genes ( Wu et al, 2009 ). It has been widely used to explore tissue- and organ-specific genes, indicating the correlated systems in diseases ( Fang et al, 2022 ; Li et al, 2022 ; Xing et al, 2022 ). According to BioGPS, the co-DEGs above were mainly expressed in the hematologic/immune system and neurologic system, which highlights the immune system’s role in neuropathic pain and aging.…”

Section: Discussionmentioning

confidence: 99%

Identification of the common differentially expressed genes and pathogenesis between neuropathic pain and aging

Huang

et al. 2022

Front. Neurosci.

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BackgroundNeuropathic pain is a debilitating disease caused by damage or diseases of the somatosensory nervous system. Previous research has indicated potential associations between neuropathic pain and aging. However, the mechanisms by which they are interconnected remain unclear. In this study, we aim to identify the common differentially expressed genes (co-DEGs) between neuropathic pain and aging through integrated bioinformatics methods and further explore the underlying molecular mechanisms.MethodsThe microarray datasets GSE24982, GSE63442, and GSE63651 were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and co-DEGs were first identified. Functional enrichment analyses, protein-protein Interaction (PPI) network, module construction and hub genes identification were performed. Immune infiltration analysis was conducted. Targeted transcription factors (TFs), microRNAs (miRNAs) and potential effective drug compounds for hub genes were also predicted.ResultsA total of 563 and 1,250 DEGs of neuropathic pain and aging were screened, respectively. 16 genes were further identified as co-DEGs. The functional analysis emphasizes the vital roles of the humoral immune response and complement and coagulation cascades in these two diseases. Cxcl14, Fblim1, RT1-Da, Serping1, Cfd, and Fcgr2b were identified as hub genes. Activated B cell, mast cell, activated dendritic cell, CD56 bright natural killer cell, effector memory CD8 + T cell, and type 2 T helper cell were significantly up-regulated in the pain and aging condition. Importantly, hub genes were found to correlate with the activated B cell, activated dendritic cell, Gamma delta T cell, central memory CD4 + T cell and mast cell in pain and aging diseases. Finally, Spic, miR-883-5p, and miR-363-5p et al. were predicted as the potential vital regulators for hub genes. Aldesleukin, Valziflocept, MGD-010, Cinryze, and Rhucin were the potential effective drugs in neuropathic pain and aging.ConclusionThis study identified co-DEGs, revealed molecular mechanisms, demonstrated the immune microenvironment, and predicted the possible TFs, miRNAs regulation networks and new drug targets for neuropathic pain and aging, providing novel insights into further research.

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Section: Discussionmentioning

confidence: 99%

Identification of the common differentially expressed genes and pathogenesis between neuropathic pain and aging

Huang

et al. 2022

Front. Neurosci.

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“…[ 52 ] In the analysis of ceRNA network construction, it was found that FOS protein may be a biomarker of gout. [ 53 ] In addition, the activation of FOS signal plays an important role in arthritic joint destruction. [ 52 ] IL-1B, IL-6 and TNF are typical proinflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

“…[ 60 ] IL-17 has been confirmed by many studies as a biomarker for the diagnosis of gout. [ 53 , 61 ] NOD-like receptor signaling pathway has long been considered to be associated with immunity, inflammation and autophagy. [ 62 ] NOD-likereceptor (NLR) is a protein family in which NLRP3 inflammatory bodies can be activated by a variety of stimuli, resulting in aseptic inflammation.…”

Section: Discussionmentioning

confidence: 99%

The combination of molecular docking and network pharmacology reveals the molecular mechanism of Danggui Niantong decoction in treating gout

Liu

Luo

2022

Medicine

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Background: Due to unhealthy diet and living habits, the incidence of gout is on the rise and has become a common disease with a high incidence. Danggui Niantong decoction (DGNTD), as a classic formula composed of 15 common herbs, has been widely used in clinical practice since ancient times to prevent and treat gout. However, the pharmacological mechanism and target of DGNTD are not clear. Methods: The potential active compounds and targets of DGNTD were obtained by traditional Chinese medicine systems pharmacology (TCMSP) database, and the differential genes of gout patients and controls were analyzed in gene expression omnibus (GEO) database. GSEA analysis of differential genes with GSEA 4.1.0 software and then the differential genes were intersected with the gout-related disease targets searched by GeneCard, CTD and OMIM disease database to obtain the final disease target. The “Traditional Chinese medicine-Active compounds-Targets” network was constructed by Cytoscape3.7.2 software. The R packet is used for enrichment analysis. The molecular docking between the active compound of DGNTD and the core target was verified by AutoDockTools software. Results: Two hundred eighty six and 244 targets of DGNTD-related active components and 652 targets of gout were obtained, of which 13 targets were potential targets of DGNTD in the treatment of gout. GSEA analysis showed that the differential genes were mainly involved in apoptosis, inflammatory reaction, and receptor metabolism and so on. Gene ontology (GO) functional enrichment analysis shows that DGNTD regulates many biological processes, such as the response to purine-containing compound and response to lipopolysaccharide, positive regulation of acute inflammatory response and other cellular components. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis shows that DGNTD treatment of gout is mainly related to interleukin-17 (IL-17), Toll-like receptor, rheumatoid arthritis, tumor necrosis factor (TNF) and so on. The results of molecular docking showed that the five active compounds in DGNTD had strong binding activity to core protein receptors. Conclusions: The active compounds of DGNTD may achieve the purpose of treating gout by acting on the core target (CASP8, CXCL8, FOS, IL1B, IL6, JUN, PTGS2, STAT1, MMP1, TNF) to regulate cell metabolism, proliferation and apoptosis, and improve inflammatory response, which is the result of multi-component, multi-target and multi-pathway interaction. It provides an idea for the development of new combined drugs for gout.

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“…Hub genes in networks were identified with the cytoHubba plugin in Cytoscape 3.9.1 ( 18 ). Hub genes were calculated with three algorithms, including Maximal Clique Centrality (MCC), Degree, and Maximum Neighborhood Component (MNC), and then presented using the Venn diagram online tool ( 19 , 20 ). The pathways related to SSc were predicted by the Comparative Toxicogenomics Database.…”

Section: Methodsmentioning

confidence: 99%

Identification of lncRNA–miRNA–mRNA networks in circulating exosomes as potential biomarkers for systemic sclerosis

et al. 2023

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ObjectiveThis study aimed to analyze potential biomarkers for systemic sclerosis (SSc) by constructing lncRNA–miRNA–mRNA networks in circulating exosomes (cirexos).Materials and methodsDifferentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in SSc cirexos were screened using high-throughput sequencing and detected with real-time quantitative PCR (RT-qPCR). Differentially expressed genes (DEGs) were analyzed using the DisGeNET, GeneCards, GSEA4.2.3, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Receiver operating characteristic (ROC) curves, correlation analyses, and a double-luciferase reporter gene detection assay were used to analyze competing endogenous RNA (ceRNA) networks and clinical data.ResultsIn this study, 286 DEmRNAs and 192 DElncRNAs were screened, of which 18 DEGs were the same as the SSc-related genes. The main SSc-related pathways included extracellular matrix (ECM) receptor interaction, local adhesion, platelet activation, and IgA production by the intestinal immune network. A hub gene, COL1A1, was obtained by a protein–protein interaction (PPI) network. Four ceRNA networks were predicted through Cytoscape. The relative expression levels of COL1A1, ENST0000313807, and NON-HSAT194388.1 were significantly higher in SSc, while the relative expression levels of hsa-miR-29a-3p, hsa-miR-29b-3p, and hsa-miR-29c-3p were significantly lower in SSc (P < 0.05). The ROC curve showed that the ENST00000313807-hsa-miR-29a-3p-COL1A1 network as a combined biomarker of SSc is more valuable than independent diagnosis, and that it is correlated with high-resolution CT (HRCT), Scl-70, C-reactive protein (CRP), Ro-52, IL-10, IgM, lymphocyte percentage, neutrophil percentage, albumin divided by globulin, urea, and RDW-SD (P < 0.05). Double-luciferase reporter gene detection showed that ENST00000313807 interacts with hsa-miR-29a-3p, which interacts with COL1A1.ConclusionThe ENST00000313807-hsa-miR-29a-3p-COL1A1 network in plasma cirexos represents a potential combined biomarker for the clinical diagnosis and treatment of SSc.

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Identification of potential biomarkers of gout through competitive endogenous RNA network analysis

Cited by 10 publications

References 45 publications

Identification of the common differentially expressed genes and pathogenesis between neuropathic pain and aging

Identification of the common differentially expressed genes and pathogenesis between neuropathic pain and aging

The combination of molecular docking and network pharmacology reveals the molecular mechanism of Danggui Niantong decoction in treating gout

Identification of lncRNA–miRNA–mRNA networks in circulating exosomes as potential biomarkers for systemic sclerosis

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