心脏毒性
RNA甲基化
基因敲除
脱甲基酶
N6-甲基腺苷
下调和上调
阿霉素
甲基化
化学
核糖核酸
细胞凋亡
小干扰RNA
甲基转移酶
癌症研究
药理学
医学
内科学
毒性
生物化学
表观遗传学
化疗
基因
作者
Pujiao Yu,Jiaqi Wang,Gui-e Xu,Xuan Zhao,Xinxin Cui,Jianxing Feng,Jiangpeng Sun,Tianhui Wang,Michail Spanos,H. Immo Lehmann,Guoping Li,Jiahong Xu,Lijun Wang,Junjie Xiao
标识
DOI:10.1016/j.jacbts.2022.12.005
摘要
Cardiac death is a major burden for cancer survivors, yet there is currently no effective treatment for doxorubicin (DOX)-induced cardiotoxicity. Here, we report that circ-ZNF609 knockdown knockdown had cardioprotective effects against DOX-induced cardiomyocyte toxicity. Mechanistically, circ-ZNF609 knockdown alleviated DOX-induced cardiotoxicity through attenuating cardiomyocyte apoptosis, reducing reactive oxygen species production, ameliorating mitochondrial nonheme iron overload. circ-ZNF609 inhibition blocked the elevation of RNA N6-methyladenosine (RNA m6A) methylation level in DOX-treated mice hearts, whereas m6A demethylase fat mass and obesity associated (FTO) acted as the downstream factor of circ-ZNF609. Moreover, the stability of circ-ZNF609 was regulated by RNA m6A methylation alteration, and suppression of RNA m6A methylation by methyltransferase like 14 (METTL14) modulated the function of circ-ZNF609. These data suggest that circ-ZNF609 inhibition represents a potential therapy for DOX-induced cardiotoxicity.
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