Brain and behavior · 2025
Unraveling the Disease Mechanisms of Neuropathic Pain Through Constructing miRNA-mRNA Networks Based on a Rat Model.
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Yao Lingqi, Liu Ming
Аннотация
BACKGROUND: Neuropathic pain (NP) lacks clear biomarkers and effective treatment methods. We aimed to identify important genes and microRNA (miRNA)-messenger RNA (mRNA) regulatory network in NP to elucidate the underlying mechanism of NP using bioinformatics analysis combined with an animal model.
METHODS: Two NP-related gene expression datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between NP and controls were identified using the limma package. Protein-protein interaction (PPI) and miRNA-mRNA-disease networks were constructed to investigate the interactions among genes and miRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to investigate the biological functions of DEGs in NP. Additionally, to further confirm the expression and the functions of hub genes, a chronic constriction injury (CCI) NP rat model was established, and C1qb knockdown treatment was performed by transfection of sh-C1qb.
RESULTS: A total of 108 common DEGs (94 upregulated and 14 downregulated) were identified related to the pathogenesis of NP. Five hub genes (Ptprc, C1qb, Aif1, Fcgr2b, and Ccl2) were selected in the PPI network. KEGG analyses unveiled that the five hub genes were primarily involved in immune regulation and neuroinflammation especially NF-κB signaling pathway. miRNA-mRNA-disease network analysis revealed 160 miRNAs associated with the five hub genes, and 25 miRNAs (including miR-124-3p, miR-128-3p, and miR-369-3p) were regulated to Ptprc, C1qb, Fcgr2b, and Ccl2 in NP. Moreover, the expressions of Aif1, Ptprc, C1qb, Fcgr2b, and Ccl2 were increased in blood, spinal cord, dorsal root ganglia, and prefrontal cortex in NP rats compared to sham rats. C1qb knockdown alleviated the rat NP and inhibited the NF-κB signaling pathway.
CONCLUSION: Four hub genes (Ptprc, C1qb, Fcgr2b, and Ccl2) may be potential biomarkers in NP pathogenesis, offering insights into its molecular mechanisms and suggesting therapeutic targets. C1qb knockdown is demonstrated to alleviate the NP progression through the NF-κB signaling pathway.
METHODS: Two NP-related gene expression datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between NP and controls were identified using the limma package. Protein-protein interaction (PPI) and miRNA-mRNA-disease networks were constructed to investigate the interactions among genes and miRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to investigate the biological functions of DEGs in NP. Additionally, to further confirm the expression and the functions of hub genes, a chronic constriction injury (CCI) NP rat model was established, and C1qb knockdown treatment was performed by transfection of sh-C1qb.
RESULTS: A total of 108 common DEGs (94 upregulated and 14 downregulated) were identified related to the pathogenesis of NP. Five hub genes (Ptprc, C1qb, Aif1, Fcgr2b, and Ccl2) were selected in the PPI network. KEGG analyses unveiled that the five hub genes were primarily involved in immune regulation and neuroinflammation especially NF-κB signaling pathway. miRNA-mRNA-disease network analysis revealed 160 miRNAs associated with the five hub genes, and 25 miRNAs (including miR-124-3p, miR-128-3p, and miR-369-3p) were regulated to Ptprc, C1qb, Fcgr2b, and Ccl2 in NP. Moreover, the expressions of Aif1, Ptprc, C1qb, Fcgr2b, and Ccl2 were increased in blood, spinal cord, dorsal root ganglia, and prefrontal cortex in NP rats compared to sham rats. C1qb knockdown alleviated the rat NP and inhibited the NF-κB signaling pathway.
CONCLUSION: Four hub genes (Ptprc, C1qb, Fcgr2b, and Ccl2) may be potential biomarkers in NP pathogenesis, offering insights into its molecular mechanisms and suggesting therapeutic targets. C1qb knockdown is demonstrated to alleviate the NP progression through the NF-κB signaling pathway.