Novel oxidative stress- and ferroptosis-related gene prognostic signature for erectile dysfunction

Abstract Background Studies have suggested that Guizhi Jia Longgu Muli decoction (GuiZhiJiaLongGuMuLiTang) has a therapeutic effect on erectile dysfunction (ED), even though how it works is still not fully understood. Methods In this research, transcriptome data related to ED were extracted from the...

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Main Authors: Meijun Liu, Maobin Yu, ZiYang Ma, Zilong Xu, Tao Zhang, Hongsen Zeng, Ze Li, XiYu Dang, Peihai Zhang
Format: Article
Language:English
Published: SpringerOpen 2024-12-01
Series:Egyptian Journal of Medical Human Genetics
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Online Access:https://doi.org/10.1186/s43042-024-00624-0
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author Meijun Liu
Maobin Yu
ZiYang Ma
Zilong Xu
Tao Zhang
Hongsen Zeng
Ze Li
XiYu Dang
Peihai Zhang
author_facet Meijun Liu
Maobin Yu
ZiYang Ma
Zilong Xu
Tao Zhang
Hongsen Zeng
Ze Li
XiYu Dang
Peihai Zhang
author_sort Meijun Liu
collection DOAJ
description Abstract Background Studies have suggested that Guizhi Jia Longgu Muli decoction (GuiZhiJiaLongGuMuLiTang) has a therapeutic effect on erectile dysfunction (ED), even though how it works is still not fully understood. Methods In this research, transcriptome data related to ED were extracted from the GEO database. The candidate target genes were obtained by intersecting the differentially expressed genes (DEGs) screened using the software package limma, oxidative stress-related genes (OSRGs), ferroptosis-related genes (FRGs), and the target genes of the chemically active ingredients of GuiZhiJiaLongGuMuLiTang. Enrichment analyses of these candidate target genes were conducted using ClusterProfiler, and the key chemically active ingredient-candidate target gene-KEGG pathway network was constructed using Cytoscape. Then, the key target genes of ED were identified through an analysis of protein–protein interactions (PPIs). Additionally, a gene set enrichment analysis (GSEA) was performed to investigate the functions of the key target genes, and the mRNA-miRNA and TF-mRNA regulatory networks were developed to explore the potential regulation of these key genes. Furthermore, the intermolecular interactions between key target genes and key chemically active ingredients of GuiZhiJiaLongGuMuLiTang were studied using molecular docking analysis. Results Fifteen candidate target genes were associated with the HIF-1 signaling pathway, of which EGFR, PPARG, SLC2A1, and SRC were screened as the key target genes for ED. Notably, these key target genes were associated with oxidative phosphorylation, focal adhesion, and ECM–receptor interaction. The miRNA-mRNA and TF-mRNA regulatory networks were constructed, and it was observed that EGR1 could regulate EGFR and PPARG, TP53 could regulate EGFR and SLC2A1, and SP1 could regulate EGFR and SRC simultaneously. The miRNAs hsa-miR-1-3p, hsa-miR-218-5p, hsa-miR-138-5p, and hsa-miR-27a-3p were the common miRNAs of EGFR and PPARG. Furthermore, quercetin was the key chemically active ingredient of GuiZhiJiaLongGuMuLiTang, with the docking affinity between SLC2A1 and quercetin being the highest. Conclusion This study identified four key target genes related to oxidative stress and ferroptosis in ED: EGFR, PPARG, SLC2A1, and SRC, along with quercetin, an active compound in GuiZhiJiaLongGuMuLiTang. These results enrich the research on the mechanism of Guizhi Jia Longgu Muli decoction in treating erectile dysfunction.
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spelling doaj-art-01f2c64628d144b79c2fbba1a410dd862025-08-20T01:57:15ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412024-12-0125111010.1186/s43042-024-00624-0Novel oxidative stress- and ferroptosis-related gene prognostic signature for erectile dysfunctionMeijun Liu0Maobin Yu1ZiYang Ma2Zilong Xu3Tao Zhang4Hongsen Zeng5Ze Li6XiYu Dang7Peihai Zhang8Department of Neurology, Hospital of Chengdu University of Traditional Chinese MedicineTCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese MedicineDepartment of Andrologic, Hospital of Chengdu University of Traditional Chinese MedicineTCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese MedicineTCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese MedicineTCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese MedicineTCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese MedicineTCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese MedicineThe Second Affiliated Hospital of Chengdu University of Traditional Chinese MedicineAbstract Background Studies have suggested that Guizhi Jia Longgu Muli decoction (GuiZhiJiaLongGuMuLiTang) has a therapeutic effect on erectile dysfunction (ED), even though how it works is still not fully understood. Methods In this research, transcriptome data related to ED were extracted from the GEO database. The candidate target genes were obtained by intersecting the differentially expressed genes (DEGs) screened using the software package limma, oxidative stress-related genes (OSRGs), ferroptosis-related genes (FRGs), and the target genes of the chemically active ingredients of GuiZhiJiaLongGuMuLiTang. Enrichment analyses of these candidate target genes were conducted using ClusterProfiler, and the key chemically active ingredient-candidate target gene-KEGG pathway network was constructed using Cytoscape. Then, the key target genes of ED were identified through an analysis of protein–protein interactions (PPIs). Additionally, a gene set enrichment analysis (GSEA) was performed to investigate the functions of the key target genes, and the mRNA-miRNA and TF-mRNA regulatory networks were developed to explore the potential regulation of these key genes. Furthermore, the intermolecular interactions between key target genes and key chemically active ingredients of GuiZhiJiaLongGuMuLiTang were studied using molecular docking analysis. Results Fifteen candidate target genes were associated with the HIF-1 signaling pathway, of which EGFR, PPARG, SLC2A1, and SRC were screened as the key target genes for ED. Notably, these key target genes were associated with oxidative phosphorylation, focal adhesion, and ECM–receptor interaction. The miRNA-mRNA and TF-mRNA regulatory networks were constructed, and it was observed that EGR1 could regulate EGFR and PPARG, TP53 could regulate EGFR and SLC2A1, and SP1 could regulate EGFR and SRC simultaneously. The miRNAs hsa-miR-1-3p, hsa-miR-218-5p, hsa-miR-138-5p, and hsa-miR-27a-3p were the common miRNAs of EGFR and PPARG. Furthermore, quercetin was the key chemically active ingredient of GuiZhiJiaLongGuMuLiTang, with the docking affinity between SLC2A1 and quercetin being the highest. Conclusion This study identified four key target genes related to oxidative stress and ferroptosis in ED: EGFR, PPARG, SLC2A1, and SRC, along with quercetin, an active compound in GuiZhiJiaLongGuMuLiTang. These results enrich the research on the mechanism of Guizhi Jia Longgu Muli decoction in treating erectile dysfunction.https://doi.org/10.1186/s43042-024-00624-0Guizhi Jia Longgu Muli decoctionFerroptosisOxidative stressErectile dysfunctionBioinformatics analysis
spellingShingle Meijun Liu
Maobin Yu
ZiYang Ma
Zilong Xu
Tao Zhang
Hongsen Zeng
Ze Li
XiYu Dang
Peihai Zhang
Novel oxidative stress- and ferroptosis-related gene prognostic signature for erectile dysfunction
Egyptian Journal of Medical Human Genetics
Guizhi Jia Longgu Muli decoction
Ferroptosis
Oxidative stress
Erectile dysfunction
Bioinformatics analysis
title Novel oxidative stress- and ferroptosis-related gene prognostic signature for erectile dysfunction
title_full Novel oxidative stress- and ferroptosis-related gene prognostic signature for erectile dysfunction
title_fullStr Novel oxidative stress- and ferroptosis-related gene prognostic signature for erectile dysfunction
title_full_unstemmed Novel oxidative stress- and ferroptosis-related gene prognostic signature for erectile dysfunction
title_short Novel oxidative stress- and ferroptosis-related gene prognostic signature for erectile dysfunction
title_sort novel oxidative stress and ferroptosis related gene prognostic signature for erectile dysfunction
topic Guizhi Jia Longgu Muli decoction
Ferroptosis
Oxidative stress
Erectile dysfunction
Bioinformatics analysis
url https://doi.org/10.1186/s43042-024-00624-0
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