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Updated: May 11, 2026
A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish
Published on: June 7, 2018
Identification of autophagy-related signatures in doxorubicin-induced cardiotoxicity
Haiyan Wu1, Haoqiang Chen2, Xiaoxue Ding2
1Faculty of Life Science and Technology, Kunming University of Science and Technology, No. 727 Jingming South Road, Kunming 650500, P.R.China; Department of Cardiovascular Medicine, The First People's Hospital of Yunnan Province/The Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Kunming 650032, P.R.China.
Purpose:
Doxorubicin is an antibiotic drug used clinically to treat infectious diseases and tumors. Unfortunately, it is cardiotoxic. Autophagy is a cellular self-decomposition process that is essential for maintaining homeostasis in the internal environment. Accordingly, the present study was proposed to characterize the autophagy-related signatures of doxorubicin-induced cardiotoxicity.
Methods:
Datasets related to doxorubicin-induced cardiotoxicity were retrieved by searching the GEO database and differentially expressed genes (DEGs) were identified. DEGs were taken to intersect with autophagy-related genes to obtain autophagy-related signatures, and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction (PPI) network were performed on them. Further, construction of miRNA-hub gene networks and identification of target drugs to reveal potential molecular mechanisms and therapeutic strategies. Animal models of doxorubicin-induced cardiotoxicity were constructed to validate differences in gene expression for autophagy-related signatures.
Results:
PBMC and heart samples from the GSE37260 dataset were selected for analysis. There were 995 and 2357 DEGs in PBMC and heart samples, respectively, and they had 23 intersecting genes with autophagy-related genes. RT-qPCR confirmed the differential expression of 23 intersecting genes in doxorubicin-induced cardiotoxicity animal models in general agreement with the bioinformatics results. An autophagy-related signatures consisting of 23 intersecting genes is involved in mediating processes and pathways such as autophagy, oxidative stress, apoptosis, protein ubiquitination and phosphorylation. Moreover, Akt1, Hif1a and Mapk3 are hub genes in autophagy-associated signatures and their upstream miRNAs are mainly rno-miR-1188-5p, rno-miR-150-3p and rno-miR-326-3p, and their drugs are mainly CHEMBL55802, Carboxyamidotriazole and 3-methyladenine.
Conclusion:
This study identifies for the first-time autophagy-related signatures in doxorubicin's cardiotoxicity, which could provide potential molecular mechanisms and therapeutic strategies for doxorubicin-induced cardiotoxicity.
Insights
This study identifies key autophagy-related gene signatures in doxorubicin-induced cardiotoxicity. These findings offer potential molecular mechanisms and novel therapeutic strategies for mitigating heart damage caused by this chemotherapy drug.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Pharmacology
Background:
- Doxorubicin is a vital chemotherapy agent but causes cardiotoxicity.
- Autophagy is a critical cellular process for maintaining homeostasis.
- Understanding doxorubicin's impact on autophagy is crucial for patient safety.
Purpose of the Study:
- To identify autophagy-related gene signatures associated with doxorubicin-induced cardiotoxicity.
- To explore the molecular mechanisms underlying this toxicity.
- To propose potential therapeutic strategies.
Main Methods:
- Bioinformatic analysis of GEO datasets (GSE37260) to identify differentially expressed genes (DEGs).
- Intersection of DEGs with autophagy-related genes to define signatures.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.
- Construction of miRNA-gene networks and identification of potential drug targets.
- Validation using animal models of doxorubicin-induced cardiotoxicity.
Main Results:
- Identified 23 autophagy-related genes as signatures in doxorubicin cardiotoxicity.
- These signatures are implicated in pathways including autophagy, oxidative stress, and apoptosis.
- Key hub genes (Akt1, Hif1a, Mapk3) and their regulatory miRNAs were identified.
- Potential therapeutic drugs (e.g., Carboxyamidotriazole) were highlighted.
Conclusions:
- This research establishes novel autophagy-related signatures for doxorubicin cardiotoxicity.
- Provides insights into molecular mechanisms and potential therapeutic interventions.
- Paves the way for developing strategies to prevent or treat doxorubicin-induced heart damage.
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