RETRACTED: MiR-22 Inhibition Alleviates Cardiac Dysfunction in Doxorubicin-Induced Cardiomyopathy by Targeting the sirt1/PGC-1α Pathway

Doxorubicin (DOX) cardiotoxicity is a life-threatening side effect that leads to a poor prognosis in patients receiving chemotherapy. We investigated the role of miR-22 in doxorubicin-induced cardiomyopathy and the underlying mechanism in vivo and in vitro. Specifically, we designed loss-of-function...

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Bibliographic Details
Main Authors: Runze Wang, Yuerong Xu, Xiaolin Niu, Yexian Fang, Dong Guo, Jiangwei Chen, Hanzhao Zhu, Jiaying Dong, Ran Zhao, Ying Wang, Bingchao Qi, Gaotong Ren, Xue Li, Li Liu, Mingming Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-04-01
Series:Frontiers in Physiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2021.646903/full
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Summary:Doxorubicin (DOX) cardiotoxicity is a life-threatening side effect that leads to a poor prognosis in patients receiving chemotherapy. We investigated the role of miR-22 in doxorubicin-induced cardiomyopathy and the underlying mechanism in vivo and in vitro. Specifically, we designed loss-of-function and gain-of-function experiments to identify the role of miR-22 in doxorubicin-induced cardiomyopathy. Our data suggested that inhibiting miR-22 alleviated cardiac fibrosis and cardiac dysfunction induced by doxorubicin. In addition, inhibiting miR-22 mitigated mitochondrial dysfunction through the sirt1/PGC-1α pathway. Knocking out miR-22 enhanced mitochondrial biogenesis, as evidenced by increased PGC-1α, TFAM, and NRF-1 expression in vivo. Furthermore, knocking out miR-22 rescued mitophagy, which was confirmed by increased expression of PINK1 and parkin and by the colocalization of LC3 and mitochondria. These protective effects were abolished by overexpressing miR-22. In conclusion, miR-22 may represent a new target to alleviate cardiac dysfunction in doxorubicin-induced cardiomyopathy and improve prognosis in patients receiving chemotherapy.
ISSN:1664-042X