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.