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. 2021 Nov 1:12:767654.
doi: 10.3389/fgene.2021.767654. eCollection 2021.

"VSports在线直播" Identification of Hub Genes and Potential ceRNA Networks of Diabetic Nephropathy by Weighted Gene Co-Expression Network Analysis

Guoqing Li  1 , Jun Zhang  1 , Dechen Liu  1 , Qiong Wei  1 , Hui Wang  1 , Yingqi Lv  1 , Zheng Ye  1 , Gaifang Liu  2 , Ling Li  1   3
Affiliations

Identification of Hub Genes and Potential ceRNA Networks of Diabetic Nephropathy by Weighted Gene Co-Expression Network Analysis

Guoqing Li et al. Front Genet. .

"VSports在线直播" Abstract

Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetic patients, and is the main cause of end-stage renal disease. The exact molecular mechanism of DN is not fully understood. The aim of this study was to identify novel biomarkers and mechanisms for DN disease progression by weighted gene co-expression network analysis (WGCNA). From the GSE142153 dataset based on the peripheral blood monouclear cells (PBMC) of DN, we identified 234 genes through WGCNA and differential expression analysis VSports手机版. Gene Ontology (GO) annotations mainly included inflammatory response, leukocyte cell-cell adhesion, and positive regulation of proteolysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways mostly included IL-17 signaling pathway, MAPK signaling pathway, and PPAR signaling pathway in DN. A total of four hub genes (IL6, CXCL8, MMP9 and ATF3) were identified by cytoscape, and the relative expression levels of hub genes were also confirmed by RT-qPCR. ROC curve analysis determined that the expression of the four genes could distinguish DN from controls (the area under the curve is all greater than 0. 8), and Pearson correlation coefficient analysis suggested that the expression of the four genes was related to estimated glomerular filtration rate (eGFR) of DN. Finally, through database prediction and literature screening, we constructed lncRNA-miRNA-mRNA network. We propose that NEAT1/XIST/KCNQ1T1-let-7b-5p-IL6, NEAT1/XIST-miR-93-5p-CXCL8 and NEAT1/XIST/KCNQ1T1-miR-27a-3p/miR-16-5p-ATF3 might be potential RNA regulatory pathways to regulate the disease progression of early DN. In conclusion, we identified four hub genes, namely, IL6, CXCL8, MMP9, and ATF3, as markers for early diagnosis of DN, and provided insight into the mechanisms of disease development in DN at the transcriptome level. .

Keywords: RNA regulatory pathways; RT-qPCR; diabetic nephropathy; hub gene; weighted gene co-expression network analysis V体育安卓版. .

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Research flow chart.
FIGURE 2
FIGURE 2
Construction of Co-Expression Network in GSE142153 by WGCNA. (A) Sample dendrogram and trait heatmap. (B) Scale independence (Left) and Mean connectivity (Right). (C) The Cluster dendrogram of co-expression network modules is ordered by a hierarchical clustering of genes based on the 1-TOM matrix. Different colors represent different modules. (D) Network heatmap plot in the co-expression modules (The progressively saturated red colors indicated higher overlap among the functional modules.).
FIGURE 3
FIGURE 3
Main findings in the module-trait correlations analyses. (A) Module-trait relationships. Each row represents a color module and every column represents a clinical trait (normal and diabetic nephropathy). Each cell contains the correlation coefficient and corresponding p value. (B) Cluster diagram of modules (Above) and heatmap of trait and modules (Below). (C) The gene significance for diabetic nephropathy in the green module (One dot represents one gene in the green module.).
FIGURE 4
FIGURE 4
Screening of differentially expressed genes (DEGs). (A) Volcano of the GSE142153 dataset with the cut-off criteria of |logFC| > 0.5 and adj.p < 0.05. (B) The Venn diagram of common DEGs (Co-DEGs) in DEGs and Green module.
FIGURE 5
FIGURE 5
Analysis results of Co-DEGs in the Gene ontology (GO) and Kyoto encyclopedia of genesand genomes pathway (KEGG). (A) Results of GO enrichment analysis of Co-DEGs. The color represents the pvalue, and the size of the spots represents the gene number. (B) Results of KEGG pathway analysis of Co-DEGs. The color represents the p-value, and the size of the spots represents the gene number.
FIGURE 6
FIGURE 6
PPI network of Co-DEGs and three cluster modules extracted by MCODE. (A) The interaction network between proteins coded by Co-DEGs was comprised of 130 nodes and 330 edges. Each node represents a protein, while each edge represents one protein–protein association. The size of the node represents the value of Degree, and the color of the node represents Neighborhood Connectivity. (B) Three cluster modules extracted by MCODE.
FIGURE 7
FIGURE 7
Screening of HUB genes and the co-expressed network of mRNAs and target miRNAs. (A) The Venn diagram of four hub genes identified by seven algorithms of cytoHubba. (B) The mRNA-miRNA co-expressed network was constructed by Cytoscape including 228 nodes and 237 edges. One node represents a mRNA or miRNA, while one edge represents one interaction of mRNA and miRNA. Yellow nodes represent the hub genes, and blue nodes represent miRNAs.
FIGURE 8
FIGURE 8
Validation and Efficacy Evaluation of HUB genes. (A) The expression of hub genes was detected by QPCR, compared with normal samples, all hub genes were upregulated in diabetic nephropathy samples with significance. (B) The expression of hub genes was negatively correlated with eGFR. (C) ROC curve of the hub genes including IL6, CXCL8, MMP9 and ATF3 in GSE142153.
FIGURE 9
FIGURE 9
Three ceRNA networks of IL6, CXCL8 and ATF3 and the potential RNA regulatory pathways. (A) ceRNA network of IL6. (B) ceRNA network of CXCL8. (C) ceRNA network of ATF3. (D) NEAT1/XIST/KCNQ1T1-let-7b-5p-IL6. (E) NEAT1/XIST-miR-93-5p-CXCL8. (F) NEAT1/XIST/KCNQ1T1-miR-27a-3p/miR-16-5p-ATF3. Diamonds represent the hub genes, circles represent miRNAs and triangle represents lncRNAs.
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References

    1. Alicic R. Z., Rooney M. T., Tuttle K. R. (2017). Diabetic Kidney Disease. Cjasn 12 (12), 2032–2045. 10.2215/cjn.11491116 - DOI - PMC - PubMed
    1. Assmann T. S., Recamonde-Mendoza M., Costa A. R., Puñales M., Tschiedel B., Canani L. H., et al. (2019). Circulating miRNAs in Diabetic Kidney Disease: Case-Control Study and In Silico Analyses. Acta Diabetol. 56 (1), 55–65. 10.1007/s00592-018-1216-x - DOI (V体育官网入口) - PubMed
    1. Catania J. M., Chen G., Parrish A. R. (2007). Role of Matrix Metalloproteinases in Renal Pathophysiologies. Am. J. Physiology-Renal Physiol. 292 (3), F905–F911. 10.1152/ajprenal.00421.2006 - DOI - PubMed
    1. Chin C.-H., Chen S.-H., Wu H.-H., Ho C.-W., Ko M.-T., Lin C.-Y. (2014). cytoHubba: Identifying Hub Objects and Sub-networks from Complex Interactome. BMC Syst. Biol. 8 (4), S11. 10.1186/1752-0509-8-s4-s11 - VSports app下载 - DOI - PMC - PubMed
    1. Chung A. C. K., Lan H. Y. (2011). Chemokines in Renal Injury. Jasn 22 (5), 802–809. 10.1681/asn.2010050510 - DOI - PubMed

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