Role of METTL3 protein in asthma: Insights from transcriptomic profiling and molecular docking analysis

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Abstract

Introduction Asthma is a chronic inflammatory disease characterized by complex immune dysregulation. This study aims to identify key m6A-related genes, particularly METTL3, as potential biomarkers and therapeutic targets in asthma. Methods Transcriptomic data from the GEO (GSE134544) dataset were analyzed to identify differentially expressed m6A-related genes. Functional enrichment analysis was performed using clusterProfiler, immune infiltration profiling was conducted with CIBERSORT, and a competing endogenous RNA (ceRNA, including miRNA and lncRNA) network was constructed. Drug enrichment analysis was carried out using DSigDB, and molecular docking was utilized to assess the interaction between Dabigatran and the METTL3 protein. Results From 192 differentially expressed genes, four m6A-related genes (METTL3, HNRNPC, IGFBP2, and RBMX) were identified as hub genes. Gene Ontology (GO) analysis revealed significant enrichment in biological processes related to RNA metabolic processes and post-transcriptional regulation, while KEGG analysis identified important pathways such as spliceosome and p53 signaling pathways. METTL3 and HNRNPC were central in the ceRNA network, interacting with miRNAs such as hsa-miR-93-3p and lncRNAs like LINC01529. Drug enrichment analysis identified Dabigatran as a potential METTL3 inhibitor, with molecular docking confirming a stable binding affinity (-5.9 kcal/mol). Conclusion This study emphasizes the critical role of m6A-related genes, particularly METTL3 and HNRNPC, as biological macromolecules in asthma pathophysiology, and provides insights into their potential as biomarkers and therapeutic targets for asthma treatment.

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