Downregulation of circ-ZNF609 Promotes Heart Repair by Modulating RNA N <sup>6</sup> -Methyladenosine-Modified <i>Yap</i> Expression
Lijun Wang, Pujiao Yu, Jiaqi Wang, Gui-e Xu, Tianhui Wang, Jingyi Feng, Yihua Bei, Jiahong Xu, Hongbao Wang, Saumya Das, Junjie Xiao
Abstract
Circular RNAs take crucial roles in several pathophysiological processes. The regulatory role and its underlying mechanisms of circ-ZNF609 in the heart remains largely unknown. Here, we report that circ-ZNF609 is upregulated during myocardial ischemia/reperfusion (I/R) remodeling. Knockdown of circ-ZNF609 protects against acute I/R injury and attenuates left ventricle dysfunction after I/R remodeling in vivo . In vitro , circ-ZNF609 regulates cardiomyocyte survival and proliferation via modulating the crosstalk between Hippo-YAP and Akt signaling. Mechanically, N 6 -methyladenosine-modification is involved in the regulatory role of circ-ZNF609 on YAP. An in-depth study indicates that knockdown of circ-ZNF609 decreases the expression of YTHDF3 and further fine-tuned the accessibility of Yap mRNA to YTHDF1 and YTHDF2 to regulate YAP expression. circ-ZNF609 knockdown represents a promising therapeutic strategy to combat the pathological process of myocardial I/R injury.