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MiR-24-3p Attenuates Doxorubicin-induced Cardiotoxicity via the Nrf2 Pathway in Mice

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Abstract

Objective

The nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) is associated with doxorubicin (DOX)-induced cardiac injury. It has been reported that microRNA-24-3p (miR-24-3p) may regulate the Keapl by mRNA degradation, whereas Keapl can suppress the activation of Nrf2. However, the role of miR-24-3p in DOX-related cardiotoxicity remains unclear.

Methods

The mice receiving DOX were used as cardiac injury model. In this study, an adenoassociated virus 9 system was used to deliver miR-24-3p or miR-scramble to mice hearts. The echocardiographic and hemodynamic analyses were used to evaluate the effects of miR-24-3p on cardiac function under DOX stimulation. ELISA and RT-PCR were used to detect protein or mRNA expressions associated with cardiac injury, inflammation response, apoptosis and oxidative stress. Western Blot were used for quantitative analysis of the roles of miR-24-3p in regulating Nrf2 expression. H9C2 cells used to verify the role of miR-24-3p in vitro.

Results

We found that miR-24-3p mRNA was significantly decreased in DOX-treated mice and cardiomyocytes. Overexpression of miR-24-3p blocked cardiac injury caused by DOX injection, as reflected by the reduction in the levels of cardiac troponin I, creatinine kinase isoenzyme MB and the N-terminal pro brain natriuretic peptide. Furthermore, miR-24-3p reduced oxidative stress and cell loss without affecting the inflammation response. As expected, we found that Nrf2 was upregulated by miR-24-3p supplementation, and that the protective efforts of miR-24-3p supplementation were abolished when Nrf2 was silenced.

Conclusion

The results from this study suggest that miR-24-3p protects cardiomyocytes against DOX-induced heart injury via activation of the Nrf2 pathway. miR-24-3p supplementation may be a novel strategy to counteract the cardiac side effects of DOX treatment.

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Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Di Fan, Hong-bin Chen & Yan Leng

  2. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430060, China

    Shi-jun Yang

  3. Department of Pulmonary and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Hong-bin Chen

  4. Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Yan Leng

Authors
  1. Di Fan
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  2. Hong-bin Chen
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  3. Yan Leng
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  4. Shi-jun Yang
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Corresponding author

Correspondence to Shi-jun Yang.

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The authors declare that they have no conflict of interest.

Additional information

This project was supported by National Natural Science Foundation of China (No. 80700289) and Medical Research Foundation of Wuhan Municipal Health Commission (No. WX19Q15).

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Fan, D., Chen, Hb., Leng, Y. et al. MiR-24-3p Attenuates Doxorubicin-induced Cardiotoxicity via the Nrf2 Pathway in Mice. CURR MED SCI 42, 48–55 (2022). https://doi.org/10.1007/s11596-022-2536-1

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  • DOI: https://doi.org/10.1007/s11596-022-2536-1

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