Wang Runze, Xu Yuerong, Niu Xiaolin, Fang Yexian, Guo Dong, Chen Jiangwei, Zhu Hanzhao, Dong Jiaying, Zhao Ran, Wang Ying, Qi Bingchao, Ren Gaotong, Li Xue, Liu Li, Zhang Mingming
Department of Cardiology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Department of Hematology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Front Physiol. 2021 Apr 1;12:646903. doi: 10.3389/fphys.2021.646903. eCollection 2021.
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 and . 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 . 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.
阿霉素（DOX）心脏毒性是一种危及生命的副作用，会导致接受化疗的患者预后不良。我们研究了miR-22在阿霉素诱导的心肌病中的作用及其潜在机制。具体而言，我们设计了功能丧失和功能获得实验，以确定miR-22在阿霉素诱导的心肌病中的作用。我们的数据表明，抑制miR-22可减轻阿霉素诱导的心脏纤维化和心脏功能障碍。此外，抑制miR-22通过sirt1/PGC-1α途径减轻线粒体功能障碍。敲除miR-22可增强线粒体生物合成，PGC-1α、TFAM和NRF-1表达增加证明了这一点。此外，敲除miR-22可挽救线粒体自噬，PINK1和parkin表达增加以及LC3与线粒体的共定位证实了这一点。过表达miR-22可消除这些保护作用。总之，miR-22可能是减轻阿霉素诱导的心肌病心脏功能障碍和改善接受化疗患者预后的新靶点。
