Open Access

DDX3X/MAVS alleviates doxorubicin‑induced cardiotoxicity by regulating stress granules

  • Authors:
    • Kaixiang Zhao
    • Shaochen Wang
    • Dandan Feng
    • Dongwei Wang
    • Guang Yang
    • Fangfang Lang
  • View Affiliations

  • Published online on: June 24, 2025     https://doi.org/10.3892/mmr.2025.13602
  • Article Number: 237
  • Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The specific mechanisms of doxorubicin (Dox)‑induced cardiotoxicity (DIC) remain unclear. In the present study, H9c2 cardiomyocytes were treated with Dox, and it was revealed that DEAD‑box RNA helicase 3 X‑linked (DDX3X), mitochondrial antiviral signaling (MAVS) and stress granules (SGs) were present at lower levels in the treated H9c2 cardiomyocytes compared with those in the control cells. The present study further investigated the mechanisms through which DIC occurs. Pretreatment with arsenite, which pharmacologically accelerates SGs, alleviated the myocardial injury caused by Dox. By contrast, anisomycin, an SG inhibitor, increased cardiomyocyte apoptosis induced by Dox. In addition, both DDX3X knockdown and pretreatment with RK‑33 (a DDX3X pharmacological inhibitor) decreased SG expression, whereas DDX3X overexpression promoted SG generation. These results indicated that DDX3X mitigated DIC through the regulation of SGs. In addition, MAVS knockdown inhibited SG assembly and reduced the expression of the anti‑apoptotic inhibitor Bcl2, and MAVS was influenced by DDX3X, thereby serving as a connector between DDX3X and SGs. The results from western blotting, reverse transcription‑quantitative PCR, immunofluorescence and flow cytometry analysis demonstrated that DDX3X, MAVS, and SGs may serve as key protective factors in DIC.
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September-2025
Volume 32 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Copy and paste a formatted citation
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Spandidos Publications style
Zhao K, Wang S, Feng D, Wang D, Yang G and Lang F: DDX3X/MAVS alleviates doxorubicin‑induced cardiotoxicity by regulating stress granules. Mol Med Rep 32: 237, 2025.
APA
Zhao, K., Wang, S., Feng, D., Wang, D., Yang, G., & Lang, F. (2025). DDX3X/MAVS alleviates doxorubicin‑induced cardiotoxicity by regulating stress granules. Molecular Medicine Reports, 32, 237. https://doi.org/10.3892/mmr.2025.13602
MLA
Zhao, K., Wang, S., Feng, D., Wang, D., Yang, G., Lang, F."DDX3X/MAVS alleviates doxorubicin‑induced cardiotoxicity by regulating stress granules". Molecular Medicine Reports 32.3 (2025): 237.
Chicago
Zhao, K., Wang, S., Feng, D., Wang, D., Yang, G., Lang, F."DDX3X/MAVS alleviates doxorubicin‑induced cardiotoxicity by regulating stress granules". Molecular Medicine Reports 32, no. 3 (2025): 237. https://doi.org/10.3892/mmr.2025.13602