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Updated: Aug 9, 2026
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Study on the potential role of KIF23 in doxorubicin-induced cardiomyopathy through multi-omics integration and
Dabao Xiao1, Zhuo Zhang1, Xin Xiao2
1The Second Affiliated Hospital of Hainan Medical University, China.
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.
Insights
Researchers identified KIF23 as a key gene in doxorubicin-induced cardiomyopathy (DIC). KIF23 may influence immune cells, particularly macrophages, offering new therapeutic targets for chemotherapy-induced heart damage.
Area of Science:
- Cardiovascular Research
- Molecular Oncology
- Immunology
Background:
- Doxorubicin (DOX) chemotherapy can cause severe cardiotoxicity, known as doxorubicin-induced cardiomyopathy (DIC).
- Understanding the molecular mechanisms underlying DIC is crucial for developing effective cardioprotective strategies.
- Identifying core genes and their immunoregulatory roles is essential for targeted therapies.
Purpose of the Study:
- To identify core genes implicated in doxorubicin-induced cardiomyopathy (DIC).
- To investigate the immunoregulatory mechanisms associated with these core genes in DIC.
- To explore potential therapeutic targets for mitigating DOX cardiotoxicity.
Main Methods:
- Integrated analysis of GEO datasets using differential expression, WGCNA, and machine learning.
- Performed functional enrichment, immune infiltration, and single-cell RNA sequencing analyses.
- Utilized AI drug screening, molecular docking, molecular dynamics, and Western blot for validation.
Main Results:
- KIF23 was identified as the central gene in DIC, linked to chromatin remodeling, cell cycle, and energy metabolism.
- DIC was associated with increased macrophages, dendritic cells, and regulatory T cells; KIF23 expression correlated negatively with immune cell infiltration.
- KIF23 is enriched in macrophages, and DOX treatment downregulated KIF23 in cardiomyocytes, with potential DOX-KIF23 binding identified.
Conclusions:
- KIF23 is a core gene in DIC, potentially mediating immune microenvironment alterations and macrophage-related pathology.
- This finding provides novel insights into DIC's molecular basis and suggests KIF23 as a potential therapeutic target.
- Further research into KIF23's role could lead to improved treatments for chemotherapy-induced cardiotoxicity.
