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

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 pr...

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Autores principales: Li, Guoqing, Zhang, Jun, Liu, Dechen, Wei, Qiong, Wang, Hui, Lv, Yingqi, Ye, Zheng, Liu, Gaifang, Li, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591079/
https://www.ncbi.nlm.nih.gov/pubmed/34790229
http://dx.doi.org/10.3389/fgene.2021.767654
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author Li, Guoqing
Zhang, Jun
Liu, Dechen
Wei, Qiong
Wang, Hui
Lv, Yingqi
Ye, Zheng
Liu, Gaifang
Li, Ling
author_facet Li, Guoqing
Zhang, Jun
Liu, Dechen
Wei, Qiong
Wang, Hui
Lv, Yingqi
Ye, Zheng
Liu, Gaifang
Li, Ling
author_sort Li, Guoqing
collection PubMed
description 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. 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.
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spelling pubmed-85910792021-11-16 Identification of Hub Genes and Potential ceRNA Networks of Diabetic Nephropathy by Weighted Gene Co-Expression Network Analysis Li, Guoqing Zhang, Jun Liu, Dechen Wei, Qiong Wang, Hui Lv, Yingqi Ye, Zheng Liu, Gaifang Li, Ling Front Genet Genetics 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. 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. Frontiers Media S.A. 2021-11-01 /pmc/articles/PMC8591079/ /pubmed/34790229 http://dx.doi.org/10.3389/fgene.2021.767654 Text en Copyright © 2021 Li, Zhang, Liu, Wei, Wang, Lv, Ye, Liu and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Li, Guoqing
Zhang, Jun
Liu, Dechen
Wei, Qiong
Wang, Hui
Lv, Yingqi
Ye, Zheng
Liu, Gaifang
Li, Ling
Identification of Hub Genes and Potential ceRNA Networks of Diabetic Nephropathy by Weighted Gene Co-Expression Network Analysis
title Identification of Hub Genes and Potential ceRNA Networks of Diabetic Nephropathy by Weighted Gene Co-Expression Network Analysis
title_full Identification of Hub Genes and Potential ceRNA Networks of Diabetic Nephropathy by Weighted Gene Co-Expression Network Analysis
title_fullStr Identification of Hub Genes and Potential ceRNA Networks of Diabetic Nephropathy by Weighted Gene Co-Expression Network Analysis
title_full_unstemmed Identification of Hub Genes and Potential ceRNA Networks of Diabetic Nephropathy by Weighted Gene Co-Expression Network Analysis
title_short Identification of Hub Genes and Potential ceRNA Networks of Diabetic Nephropathy by Weighted Gene Co-Expression Network Analysis
title_sort identification of hub genes and potential cerna networks of diabetic nephropathy by weighted gene co-expression network analysis
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591079/
https://www.ncbi.nlm.nih.gov/pubmed/34790229
http://dx.doi.org/10.3389/fgene.2021.767654
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