2. Academic Validation
  3. DDX3X alleviates doxorubicin-induced cardiotoxicity by regulating Wnt/β-catenin signaling pathway in an in vitro model

DDX3X alleviates doxorubicin-induced cardiotoxicity by regulating Wnt/β-catenin signaling pathway in an in vitro model

  • J Biochem Mol Toxicol. 2022 Aug;36(8):e23077. doi: 10.1002/jbt.23077.
Dandan Feng 1,  Jiang Li 1,  Liang Guo 2,  Jing Liu 3,  Shaochen Wang 4,  Xiuyuan Ma 1,  Yunxuan Song 4,  Ju Liu 3,  Enkui Hao 1
Affiliations

Affiliations

  • 1 Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 2 Department of Anesthesiology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China.
  • 3 Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.
  • 4 Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong First Medical University, Jinan, China.
PMID: 35467791 DOI: 10.1002/jbt.23077
Abstract

The life-threatening adverse effects of doxorubicin (Dox) caused by its cardiotoxic properties limit its clinical application. DDX3X has been shown to participate in a variety of physiological processes, and it acts as a regulator of Wnt/β-catenin signaling. However, the role of DDX3X in Dox-induced cardiotoxicity (DIC) remains unclear. In this study, we found that DDX3X expression was significantly decreased in H9c2 cardiomyocytes treated with Dox. Ddx3x knockdown and RK-33 (DDX3X ATPase activity inhibitor) pretreatment exacerbated cardiomyocyte Apoptosis and mitochondrial dysfunction induced by Dox treatment. In contrast, Ddx3x overexpression ameliorated the DIC response. Moreover, Wnt/β-catenin signaling in cardiomyocytes treated with Dox was suppressed, but this suppression was reversed by Ddx3x overexpression. Overall, this study demonstrated that DDX3X plays a protective role in DIC by activating Wnt/β-catenin signaling.

Keywords

DDX3X; Wnt/β-catenin; apoptosis; cardiotoxicity; doxorubicin.

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