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.
基金：
Yunnan Health Training Project of High Level Talents [H-2019069]; Yunnan Provincial Department of Science and Technology-Kunming Medical University Joint Special Project on Applied Basic Research [202201AY070001-257, 202401AY070001-310]; Open Project of Yunnan Provincial Cardiac Clinical Medicine Center [2022LCZXKF-X203]
第一作者机构：[1]Kunming Univ Sci & Technol, Fac Life Sci & Technol, 727 Jingming South Rd, Kunming 650500, Peoples R China[2]Kunming Univ Sci & Technol, Peoples Hosp Yunnan Prov 1, Dept Cardiovasc Med, Affiliated Hosp, 157 Jinbi Rd, Kunming 650032, Peoples R China
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推荐引用方式(GB/T 7714)：
Wu Haiyan,Chen Haoqiang,Ding Xiaoxue,et al.Identification of autophagy-related signatures in doxorubicin-induced cardiotoxicity[J].TOXICOLOGY AND APPLIED PHARMACOLOGY.2024,491:doi:10.1016/j.taap.2024.117082.
APA：
Wu, Haiyan,Chen, Haoqiang,Ding, Xiaoxue,Kuang, Xiaohui,Pang, Mingjie...&Zhang, Hong.(2024).Identification of autophagy-related signatures in doxorubicin-induced cardiotoxicity.TOXICOLOGY AND APPLIED PHARMACOLOGY,491,
MLA：
Wu, Haiyan,et al."Identification of autophagy-related signatures in doxorubicin-induced cardiotoxicity".TOXICOLOGY AND APPLIED PHARMACOLOGY 491.(2024)
