ArticleSignal transduction and targeted therapy2025
Exosomal transfer of pro-pyroptotic miR-216a-5p exacerbates anthracycline cardiotoxicity through breast cancer-heart pathological crosstalk.
Article in Signal transduction and targeted therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed.
- A multi-level charged micelle-based microneedle transdermal system for immunosuppressive tumor microenvironment regulation and synergistic therapy.Materials today. Bio · 2026Article
- Hexokinase-3 upregulation and histone H3K18 lactylation mediate murine liver fibrosis induced by Echinococcus multilocularis.PLoS neglected tropical diseases · 2026Article
- Identification of Candidate mRNA and miRNA Molecules Associated with Tuberculosis Through Preliminary Analysis and Validation Using Clinical Samples.International journal of molecular sciences · 2026Article
- Tumor exosomes impact functional hallmarks of cancer.Cancer metastasis reviews · 2026Review
- MiR-499-5P/PACS2/TRPV1 Axis Maintains Mitochondrial Homeostasis and Left Ventricular Function after Extreme Cold Stress.Journal of cardiovascular translational research · 2026Article
- Cardiac PTN-SIRT1 axis alleviates oxidative stress and promotes mitochondrial energy reprogramming to mitigate doxorubicin-induced cardiotoxicity through AMPK/PGC1α signaling.Acta biochimica et biophysica Sinica · 2026Article
- Healthy young human plasma-derived exosomes enhance neural stem cell therapy by suppressing pyroptosis via TXNIP/NLRP3 after intracerebral hemorrhage.Journal of nanobiotechnology · 2026Article
- The mechanisms and therapeutic advances of interactions between breast cancer and cardiovascular diseases.Frontiers in pharmacology · 2026Review
- Artificial intelligence in cardio-oncology: decoding mechanisms, predicting toxicity, and personalizing cancer therapy.Frontiers in cardiovascular medicine · 2026Review
- Extracellular Vesicle-Based Strategies for the Prevention of Chemotherapy-Induced Cardiotoxicity.Therapeutics and clinical risk management · 2026Review
- Cardiovascular Disease Meets Cancer: Exploring the Epidemiology in China and Homotherapy Targeting Intersectional Mechanisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Doxorubicin-Induced Cardiotoxicity: A Comprehensive Update.Journal of cardiovascular development and disease · 2025Review
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15 authors.
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Abstract
Doxorubicin (DOX) is the most effective chemotherapeutic for breast cancer, but it is usually associated with severe cardiotoxicity. Further investigation to alleviate its side effects is essential. The present study investigated the mechanism of the cross-organ communication between tumors and the heart and potential intervention targets. Morphological bubble-like protrusions were observed in both adult murine ventricular cardiomyocytes (AMVCs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) cocultured with breast cancer cells (BCCs), along with elevated expression of pyroptosis-related proteins. Exosomes (EXOs) from DOX-treated BCCs aggravated DOX-induced cardiotoxicity (DOXIC) in an orthotopic mouse model of breast cancer. Blocking miRNAs by knocking down Rab27a or inhibiting the release of EXOs in cancer tissue by Dicer enzyme knockout attenuated this additional injury effect. Exosomal miRNA sequencing revealed that miR-216a-5p is especially upregulated in EXOs from DOX-induced BCCs. Mechanistically, miR-216a-5p was upregulated by enhanced transcription mediated by DOX-induced AMP-dependent transcription factor 3 (ATF3) and packaged into EXOs by splicing factor 3b subunit 4 (SF3B4) in BCCs. Itchy E3 ubiquitin-protein ligase (ITCH) was identified as a novel downstream target mRNA of miR-216a-5p. ITCH negatively mediated thioredoxin-interacting protein (TXNIP) ubiquitination to activate the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome pathway, ultimately leading to cardiomyocyte pyroptosis. Our findings revealed novel cross-organ pathogenic communication between breast cancer and the heart through the exosomal miR-216a-5p-mediated ITCH/TXNIP/NLRP3 pathway, which drives cardiomyocyte pyroptosis. These findings suggest that targeting myocardial miR-216a-5p or blocking harmful EXOs from breast cancer is a potential therapeutic strategy for alleviating DOXIC.
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