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<p>The gut microbiome plays a crucial role in renal diseases, influencing conditions such as renal cell carcinoma (RCC), acute kidney injuries, and diabetic nephropathy. Recent studies highlight the association between gut microbial metabolites (GMM) and RCC progression. This study employs a computational network pharmacology framework to explore the mechanistic action of gut microbiota-derived metabolites against RCC. GMM were selected from the gutMgene database and analyzed for common targets using DisGeNET, Gene Card, and OMIM. Downstream analysis included gene ontology, KEGG pathway enrichment, metabolite-target-pathway-disease network construction, and protein–protein interaction analysis. Further, key metabolites were evaluated for drug-likeness, ADMET properties, and molecular docking, followed by molecular dynamics simulations (MDS) to assess complex stability. The JUN/AP-1 gene emerged as the prime target, exhibiting the highest binding affinity with Icaritin (−&#xa0;5.9&#xa0;kcal/mol), followed by Quercetin and Luteolin. MDS confirmed the stable binding of Icaritin to the active site throughout the simulation. These GMM may influence anticancer activity through distinct regulatory pathways involving the JUN/AP-1 gene, either by inhibiting or modulating its function. These insights establish a basis for further in vitro and in vivo investigations, supporting the development of microbiome-based therapeutic approaches.</p> Graphical abstract <p>The graphical abstract illustrates a computational network pharmacology and computer-aided analysis approach to investigating gut microbiota-derived metabolites in renal cell carcinoma (RCC). It highlights core target genes, gene ontology, KEGG pathways, and network analyses. The right section depicts gut microbiota, specifically <i>Bacterium sp. MRG-PMF-1</i> produces Icaritin, which inhibits the JUN gene, potentially suppressing RCC progression. Molecular docking and molecular dynamics simulations confirm stable binding interactions, supporting Icaritin’s therapeutic potential.</p> <p></p>

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Gut microbial metabolites targeting JUN in renal cell carcinoma via IL-17 signaling pathway: network pharmacology approach

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月18日

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  • Stany Bala Kumar,
  • Shatakshi Mishra,
  • Anushka Das,
  • Sagnik Nag,
  • Rakesh Naidu

摘要

The gut microbiome plays a crucial role in renal diseases, influencing conditions such as renal cell carcinoma (RCC), acute kidney injuries, and diabetic nephropathy. Recent studies highlight the association between gut microbial metabolites (GMM) and RCC progression. This study employs a computational network pharmacology framework to explore the mechanistic action of gut microbiota-derived metabolites against RCC. GMM were selected from the gutMgene database and analyzed for common targets using DisGeNET, Gene Card, and OMIM. Downstream analysis included gene ontology, KEGG pathway enrichment, metabolite-target-pathway-disease network construction, and protein–protein interaction analysis. Further, key metabolites were evaluated for drug-likeness, ADMET properties, and molecular docking, followed by molecular dynamics simulations (MDS) to assess complex stability. The JUN/AP-1 gene emerged as the prime target, exhibiting the highest binding affinity with Icaritin (− 5.9 kcal/mol), followed by Quercetin and Luteolin. MDS confirmed the stable binding of Icaritin to the active site throughout the simulation. These GMM may influence anticancer activity through distinct regulatory pathways involving the JUN/AP-1 gene, either by inhibiting or modulating its function. These insights establish a basis for further in vitro and in vivo investigations, supporting the development of microbiome-based therapeutic approaches.

Graphical abstract

The graphical abstract illustrates a computational network pharmacology and computer-aided analysis approach to investigating gut microbiota-derived metabolites in renal cell carcinoma (RCC). It highlights core target genes, gene ontology, KEGG pathways, and network analyses. The right section depicts gut microbiota, specifically Bacterium sp. MRG-PMF-1 produces Icaritin, which inhibits the JUN gene, potentially suppressing RCC progression. Molecular docking and molecular dynamics simulations confirm stable binding interactions, supporting Icaritin’s therapeutic potential.