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Expression Profile of Pyroptosis-Related Genes and the Associated Regulatory Axis in Primary Gout Patients
Shaowei Niu1,2,3, Tian-Yi Lei2,3, Fei Dai2,3
1The First Affiliated Hospital, Jinan University, Guangzhou, People's Republic of China.
Purpose:
Analyzed the expression characteristics of pyroptosis-related genes (PRGs) in peripheral blood mononuclear cells (PBMCs) of gout patients by microarray, and constructed ceRNA network to explore the molecular mechanism of RNA-mediated pyroptosis regulation.
Patients And Methods:
Human mRNA, lncRNA, circRNA microarray data were used to identify differentially expressed in PBMCs from patients with primary gout and healthy controls. Differential PRGs in PBMCs of gout patients identified by Genecard database and mRNA microarray data. GO and KEGG enrichment analyses of these genes were then conducted. Protein-protein interaction networks and cytoHubba were used to identify hub genes. Combining the lncRNA and circRNA microarray data, a ceRNA network was constructed by Cytoscape to screen out key non-coding RNA molecules that can regulate target PRGs. Finally, the relative expression levels of target miRNA and circRNA in 60 gout patients and 40 healthy subjects were detected by qRT-PCR.
Results:
The results revealed 30 differentially expressed PRGs. GO and KEGG analysis of these genes were mainly concentrated in the production and regulation of cytokines, NOD-like receptor signaling pathway and so on. Nine hub genes were screened by PPI network, including IL1B, DDX3X, NLRP3, NLRP9, AIM2, CASP8, P2XR7, CARD8 and IFI16. The has_circRNA_102906\hsa_circRNA_102910\hsa_circRNA_102911-hsa-miR-129-5p-DDX3X\NLRP3\NLRP9 regulatory network was constructed. The expression of has_circRNA_102906, hsa_circRNA_102910, hsa_circRNA_102911 were up-regulated and hsa-miR-129-5p down-regulated in PBMCs of gout patients. The relative expression of hsa_circRNA_102911 was positively correlated with clinical inflammatory indicators associated with gout, and the area under the curve of hsa_circRNA_102911 for gout diagnosis was 0.85 (95% CI: 0.775-0.925; p < 0.001).
Conclusion:
There are several differentially expressed PRGs in PBMCs of gout patients, which are involved in the regulation of gout inflammation through multiple pathways. hsa_circRNA_102911-hsa-miR-129-5p-DDX3X\NLRP3\NLRP9 may be the key regulatory pathway for pyroptosis to regulate gout inflammation, and hsa_circRNA_102911 may be a potential biomarker for the diagnosis of primary gout.
Insights
Pyroptosis-related genes (PRGs) are dysregulated in gout patients, influencing inflammation via multiple pathways. The circRNA hsa_circRNA_102911 may serve as a diagnostic biomarker for gout.
Area of Science:
- Molecular Biology
- Genetics
- Immunology
Background:
- Pyroptosis, a programmed cell death, plays a role in inflammatory diseases.
- Gout is a metabolic inflammatory disease characterized by hyperuricemia and urate crystal deposition.
- Understanding the molecular mechanisms of pyroptosis in gout is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the expression profiles of pyroptosis-related genes (PRGs) in peripheral blood mononuclear cells (PBMCs) of gout patients.
- To construct a competing endogenous RNA (ceRNA) network to elucidate the RNA-mediated regulatory mechanisms of pyroptosis in gout.
- To identify potential diagnostic biomarkers for primary gout.
Main Methods:
- Microarray analysis of mRNA, lncRNA, and circRNA in PBMCs from gout patients and healthy controls.
- Bioinformatic analyses including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment.
- Protein-protein interaction (PPI) network construction and ceRNA network analysis using Cytoscape.
- Quantitative real-time PCR (qRT-PCR) validation of key miRNA and circRNA expression levels.
Main Results:
- Thirty differentially expressed PRGs were identified, primarily involved in cytokine production and the NOD-like receptor signaling pathway.
- Nine hub genes, including IL1B, NLRP3, and CASP8, were identified through PPI network analysis.
- A ceRNA network involving has_circRNA_102906/102910/102911, hsa-miR-129-5p, and target genes DDX3X/NLRP3/NLRP9 was constructed.
- Upregulated has_circRNA_102906/102910/102911 and downregulated hsa-miR-129-5p were observed in gout patients' PBMCs.
- hsa_circRNA_102911 expression positively correlated with gout inflammatory indicators, showing a diagnostic area under the curve of 0.85.
Conclusions:
- Dysregulated PRGs in PBMCs contribute to gout inflammation through various pathways.
- The hsa_circRNA_102911-hsa-miR-129-5p-DDX3X/NLRP3/NLRP9 axis represents a key regulatory pathway in gout pathogenesis.
- hsa_circRNA_102911 holds potential as a diagnostic biomarker for primary gout.
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