Circular RNAs(circRNAs)are differentially expressed in cardiac hypertrophy;however,the exact function and mechanisms during hypertrophy development are still unknown.Here,we explored the role of a newly discovered cir...Circular RNAs(circRNAs)are differentially expressed in cardiac hypertrophy;however,the exact function and mechanisms during hypertrophy development are still unknown.Here,we explored the role of a newly discovered circRNA in the pathogenesis of myocardial hypertrophy.It was found that circ-0001283 promoted the progression of cardiac hypertrophy by interacting with myosin light chain 3(MYL3)to inhibit the protein ubiquitination and enhance its protein expression,not by the competitive endogenous RNA mechanism.Further investigation demonstrated that the reduced hypertrophy induced by circ-0001283 knockdown was counteracted by overexpression of MYL3.Mechanistically,MYL3 facilitated myocardial hypertrophy by inducing autophagy in cells via PI3K/Akt/mTOR and ERK signaling pathways.In summary,circ-0001283 can bind directly to MYL3 and up-regulate its expression,thereby promoting autophagy to accelerate cardiac hypertrophy.Circ-0001283 may serve as a potential therapeutic target for cardiac hypertrophy.展开更多
基金financially supported by the National Natural Science Foundation of China(82100251)and Gusu Talent Program(GSWS2022039).
文摘Circular RNAs(circRNAs)are differentially expressed in cardiac hypertrophy;however,the exact function and mechanisms during hypertrophy development are still unknown.Here,we explored the role of a newly discovered circRNA in the pathogenesis of myocardial hypertrophy.It was found that circ-0001283 promoted the progression of cardiac hypertrophy by interacting with myosin light chain 3(MYL3)to inhibit the protein ubiquitination and enhance its protein expression,not by the competitive endogenous RNA mechanism.Further investigation demonstrated that the reduced hypertrophy induced by circ-0001283 knockdown was counteracted by overexpression of MYL3.Mechanistically,MYL3 facilitated myocardial hypertrophy by inducing autophagy in cells via PI3K/Akt/mTOR and ERK signaling pathways.In summary,circ-0001283 can bind directly to MYL3 and up-regulate its expression,thereby promoting autophagy to accelerate cardiac hypertrophy.Circ-0001283 may serve as a potential therapeutic target for cardiac hypertrophy.
