ORIGINAL RESEARCH article
Front. Genet.
Sec. Computational Genomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1598835
Integrative bioinformatics analysis and experimental validation reveals key genes and regulatory mechanisms in the development of gout
Provisionally accepted
- 1Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- 2First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan Province, China
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Background & Aims: Gout is a prevalent inflammatory arthropathy caused by monosodium urate crystal deposition, yet its molecular pathogenesis remains incompletely understood. This study aimed to identify key genes and elucidate regulatory mechanisms underlying gout development through bioinformatics analysis combined with experimental validation.Methods: Transcriptome dataset GSE160170 and single-cell dataset GSE211783 were analyzed using differential expression analysis and weighted gene co-expression network analysis (WGCNA). Functional enrichment, protein-protein interaction (PPI), ceRNA, and transcription factor networks were constructed. Immune cell infiltration was analyzed using CIBERSORTx. Molecular docking predicted therapeutic compounds. Experimental validation included qRT-PCR, Western blot, gene knockdown/overexpression, and functional assays.Results: Among 329 gout-related genes identified, CXCL8, PTGS2, and IL10 emerged as key regulators involved in cell-cell adhesion, leukocyte activation, and NF-κB signaling. Immune infiltration revealed significant upregulation of M2 macrophages, activated mast cells, activated NK cells, and γδ T cells in gout samples.CeRNA network identified KCNQ1OT1 and hsa-mir-98-5p as regulatory elements, while CEBPB, STAT3, RELA, and NFKB1 were key transcription factors. Molecular docking suggested pergolide as a therapeutic candidate. Single-cell analysis confirmed high expression of key genes in T/NK cells and myeloid cells. Western blot validation showed upregulated protein expression of key genes in the gout model. PTGS2 knockdown enhanced cell viability and reduced apoptosis, while overexpression promoted inflammatory cytokine production and NF-κB pathway activation.This study systematically elucidated the pivotal roles of CXCL8, PTGS2, and IL10 in gout pathogenesis, providing valuable molecular targets for therapeutic development.
Keywords: Gout, ceRNA network, Immune infiltration, molecular docking, Apoptosis, Inflammatory
Received: 26 Mar 2025; Accepted: 02 Jun 2025.
Copyright: © 2025 Yuan, Guo, Gao, 陈 and Liu. 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) or licensor 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.
* Correspondence:
Ye Yuan, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
Zhou Jing Guo, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan Province, China
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