ArticleStem cell reports2022
RARG S427L attenuates the DNA repair response to doxorubicin in induced pluripotent stem cell-derived cardiomyocytes.
Article in Stem cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Doxorubicin-Induced Cardiotoxicity in Breast Cancer: Mechanistic Pathways, Pharmacogenomic Modifiers, and Translational Strategies.Cardiovascular toxicology · 2026Review
- DHDK, a Plant-Derived Natural Small Molecule, Protects Against Doxorubicin-Induced Cardiotoxicity via the PPARG-CPT1B-FAO Axis.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Ligustrazine nano-drug delivery system ameliorates doxorubicin-mediated myocardial injury via piezo-type mechanosensitive ion channel component 1-prohibitin 2-mediated mitochondrial quality surveillance.Journal of nanobiotechnology · 2025Article
- Understanding the Mechanisms of Chemotherapy-Related Cardiotoxicity Employing hiPSC-Derived Cardiomyocyte Models for Drug Screening and the Identification of Genetic and Epigenetic Variants.International journal of molecular sciences · 2025Review
- Dissecting cardiovascular disease-associated noncoding genetic variants using human iPSC models.Stem cell reports · 2025Review
- Cardiovascular Toxicity in Cancer Therapy: Protecting the Heart while Combating Cancer.Current cardiology reports · 2024Review
- Risk of anthracycline-induced cardiac dysfunction in adolescent and young adult (AYA) cancer survivors: role of genetic susceptibility loci.The pharmacogenomics journal · 2024Article
- Predicting oncology drug-induced cardiotoxicity with donor-specific iPSC-CMs-a proof-of-concept study with doxorubicin.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Anthracyclines induce cardiotoxicity through a shared gene expression response signature.PLoS genetics · 2024Article
- Anthracycline Toxicity: Light at the End of the Tunnel?Annual review of pharmacology and toxicology · 2024Review
- Analysis and Validation of Critical Signatures and Immune Cell Infiltration Characteristics in Doxorubicin-Induced Cardiotoxicity by Integrating Bioinformatics and Machine Learning.Journal of inflammation research · 2024Article
- hiPSC-derived cardiomyocytes as a model to study the role of small-conductance CaFrontiers in cell and developmental biology · 2024Review
- An integrative review of nonobvious puzzles of cellular and molecular cardiooncology.Cellular & molecular biology letters · 2023Review
- Pharmacogenomics in drug-induced cardiotoxicity: Current status and the future.Frontiers in cardiovascular medicine · 2022Review
- Current Status and Trends of Research on Anthracycline-Induced Cardiotoxicity from 2002 to 2021: A Twenty-Year Bibliometric and Visualization Analysis.Oxidative medicine and cellular longevity · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Doxorubicin is a commonly used chemotherapeutic drug, but its use is limited by doxorubicin-induced cardiotoxicity (DIC), which can lead to irreversible heart failure and death. A missense variant rs2229774 (p.S427L) in the retinoic acid receptor gamma (RARG) gene is associated with increased susceptibility to DIC, but the precise mechanism underlying this association is incompletely understood. We performed molecular dynamic simulations to determine the effect of this variant on RARG structure and then validated these predictions using CRISPR-Cas9-genome-edited, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). We found that this variant leads to reduced activation of its target genes in response to doxorubicin, including gene pathways involved in DNA repair and consequently an inability to mediate DNA repair after exposure to doxorubicin. Our findings establish a role of RARG p.S427L in attenuating DNA repair in DIC and provide insight into the pathogenesis of this cardiotoxic effect.
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Registered trials
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