Ferroptosis-related genes, a novel therapeutic target for focal segmental glomerulosclerosis

Abstract Recent studies have suggested that ferroptosis participates in various renal diseases. However, its effect on focal segmental glomerulosclerosis remains unclear. This study analyzed the GSE125779 and GSE121211 datasets to identify the differentially expressed genes (DEGs) in renal tubular s...

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Main Authors: Yanbin Lin, Jinxuan He, Zhixiang Mou, Huiting Chen, Wenkang You, Tianjun Guan, Lan Chen
Format: Article
Language:English
Published: BMC 2024-02-01
Series:BMC Nephrology
Subjects:
Online Access:https://doi.org/10.1186/s12882-024-03490-5
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author Yanbin Lin
Jinxuan He
Zhixiang Mou
Huiting Chen
Wenkang You
Tianjun Guan
Lan Chen
author_facet Yanbin Lin
Jinxuan He
Zhixiang Mou
Huiting Chen
Wenkang You
Tianjun Guan
Lan Chen
author_sort Yanbin Lin
collection DOAJ
description Abstract Recent studies have suggested that ferroptosis participates in various renal diseases. However, its effect on focal segmental glomerulosclerosis remains unclear. This study analyzed the GSE125779 and GSE121211 datasets to identify the differentially expressed genes (DEGs) in renal tubular samples with and without FSGS. The Cytoscape was used to construct the protein–protein interaction network. Moreover, the ferroptosis-related genes (FRGs) were obtained from the ferroptosis database, while ferroptosis-related DEGs were obtained by intersection with DEGs. The target genes were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The GSE108112 dataset was used to verify the expression of target FRGs. Besides, we built the mRNA-miRNA network regarding FRGs using the NetworkAnalyst database, and circRNAs corresponding to key miRNAs were predicted in the ENCORI database. In this study, 16 ferroptosis-related DEGs were identified between FSGS and healthy subjects, while five co-expressed genes were obtained by three topological algorithms in Cytoscape. These included the most concerned Hub genes JUN, HIF1A, ALB, DUSP1 and ATF3. The KEGG enrichment analysis indicated that FRGs were associated with mitophagy, renal cell carcinoma, and metabolic pathways. Simultaneously, the co-expressed hub genes were analyzed to construct the mRNA-miRNA interaction network and important miRNAs such as hsa-mir-155-5p, hsa-mir-1-3p, and hsa-mir-124-3p were obtained. Finally, 75 drugs targeting 54 important circRNAs and FRGs were predicted. This study identified the Hub FRGs and transcriptomic molecules from FSGS in renal tubules, thus providing novel diagnostic and therapeutic targets for FSGS.
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spelling doaj.art-0a6720733d0e45b685b9e64f0a6d0c8d2024-03-05T17:57:10ZengBMCBMC Nephrology1471-23692024-02-0125111210.1186/s12882-024-03490-5Ferroptosis-related genes, a novel therapeutic target for focal segmental glomerulosclerosisYanbin Lin0Jinxuan He1Zhixiang Mou2Huiting Chen3Wenkang You4Tianjun Guan5Lan Chen6Department of Nephrology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen UniversityDepartment of Nephrology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen UniversityDepartment of Nephrology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen UniversityFujian Medical UniversityFujian Medical UniversityDepartment of Nephrology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen UniversityDepartment of Nephrology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen UniversityAbstract Recent studies have suggested that ferroptosis participates in various renal diseases. However, its effect on focal segmental glomerulosclerosis remains unclear. This study analyzed the GSE125779 and GSE121211 datasets to identify the differentially expressed genes (DEGs) in renal tubular samples with and without FSGS. The Cytoscape was used to construct the protein–protein interaction network. Moreover, the ferroptosis-related genes (FRGs) were obtained from the ferroptosis database, while ferroptosis-related DEGs were obtained by intersection with DEGs. The target genes were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The GSE108112 dataset was used to verify the expression of target FRGs. Besides, we built the mRNA-miRNA network regarding FRGs using the NetworkAnalyst database, and circRNAs corresponding to key miRNAs were predicted in the ENCORI database. In this study, 16 ferroptosis-related DEGs were identified between FSGS and healthy subjects, while five co-expressed genes were obtained by three topological algorithms in Cytoscape. These included the most concerned Hub genes JUN, HIF1A, ALB, DUSP1 and ATF3. The KEGG enrichment analysis indicated that FRGs were associated with mitophagy, renal cell carcinoma, and metabolic pathways. Simultaneously, the co-expressed hub genes were analyzed to construct the mRNA-miRNA interaction network and important miRNAs such as hsa-mir-155-5p, hsa-mir-1-3p, and hsa-mir-124-3p were obtained. Finally, 75 drugs targeting 54 important circRNAs and FRGs were predicted. This study identified the Hub FRGs and transcriptomic molecules from FSGS in renal tubules, thus providing novel diagnostic and therapeutic targets for FSGS.https://doi.org/10.1186/s12882-024-03490-5BioinformaticsFerroptosisFocal segmental glomerulosclerosis (FSGS)Renal tubule
spellingShingle Yanbin Lin
Jinxuan He
Zhixiang Mou
Huiting Chen
Wenkang You
Tianjun Guan
Lan Chen
Ferroptosis-related genes, a novel therapeutic target for focal segmental glomerulosclerosis
BMC Nephrology
Bioinformatics
Ferroptosis
Focal segmental glomerulosclerosis (FSGS)
Renal tubule
title Ferroptosis-related genes, a novel therapeutic target for focal segmental glomerulosclerosis
title_full Ferroptosis-related genes, a novel therapeutic target for focal segmental glomerulosclerosis
title_fullStr Ferroptosis-related genes, a novel therapeutic target for focal segmental glomerulosclerosis
title_full_unstemmed Ferroptosis-related genes, a novel therapeutic target for focal segmental glomerulosclerosis
title_short Ferroptosis-related genes, a novel therapeutic target for focal segmental glomerulosclerosis
title_sort ferroptosis related genes a novel therapeutic target for focal segmental glomerulosclerosis
topic Bioinformatics
Ferroptosis
Focal segmental glomerulosclerosis (FSGS)
Renal tubule
url https://doi.org/10.1186/s12882-024-03490-5
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