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 upregul...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,N6-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.展开更多
基金the National Key Research and Development Project(2018YFE0113500 to J.J.X.)National Natural Science Foundation of China(82020108002 and 81911540486 to J.J.X.,81800358 to L.J.W.,and 82070411 to J.H.X.)+3 种基金Innovation Program of Shanghai Municipal Education Commission(2017-01-07-00-09-E00042 to J.J.X.)Science and Technology Commission of Shanghai Municipality(20DZ2255400 and 21XD1421300 to J.J.X.)“Dawn”Program of Shanghai Municipal Education Com mission(19SG34 to J.J.X.)Natural Science Foundation of Shanghai(19ZR1474100 to L.J.W.and 19ZR1450400 to H.B.W.).
文摘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,N6-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.
