Study on the potential role of KIF23 in doxorubicin-induced cardiomyopathy through multi-omics integration and AI-based screening.

OBJECTIVE: Doxorubicin-induced cardiomyopathy (DIC) is a common and severe cardiotoxic effect of doxorubicin (DOX)-based chemotherapy. This study aimed to identify core genes associated with DIC and investigate their immunoregulatory mechanisms. METHODS: Core genes were identified based on GEO datasets by integrating differential expression analysis, WGCNA, and machine learning algorithms. Functional enrichment analysis, immune infiltration analysis, and single-cell RNA sequencing analysis were subsequently performed. In addition, AI-based drug screening, molecular docking, molecular dynamics simulation, and Western blot validation were conducted. RESULTS: KIF23 was identified as the core gene. Functional analysis of DIC-related genes indicated that they were mainly involved in chromatin remodeling, cell cycle regulation, and energy metabolism. Immune infiltration analysis revealed significant enrichment of macrophages, dendritic cells, and regulatory T cells in the DIC group, and KIF23 expression was negatively correlated with multiple immune cell infiltrations. Single-cell analysis showed that KIF23 was predominantly enriched in macrophage populations. AI-based drug screening identified BRD-K40329609 as a potential therapeutic candidate. Molecular docking and 100 ns molecular dynamics simulations suggested a potential binding affinity between DOX and KIF23. In vitro experiments further demonstrated that DOX significantly downregulated KIF23 expression in cardiomyocytes. CONCLUSION: This study identified KIF23 as a core gene associated with DIC and suggested that it may be involved in immune microenvironment remodeling and macrophage-related pathological processes, providing new insights into the molecular mechanisms of DIC and potential therapeutic targets.