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Published on: August 8, 2022
Circ-0001283 Aggravates Cardiac Hypertrophy by Targeting Myosin Light Chain 3 Protein
Wenjing Wang1, Lili Chen2, Yiheng Zhao3
1Intensive Care Unit, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Insights
Circular RNAs (circRNAs) promote cardiac hypertrophy by stabilizing myosin light chain 3 (MYL3) protein, increasing cellular autophagy. This circRNA, circ-0001283, represents a potential therapeutic target for heart conditions.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- Epigenetics
Background:
- Circular RNAs (circRNAs) show altered expression in cardiac hypertrophy.
- The specific roles and mechanisms of circRNAs in hypertrophy pathogenesis remain largely unknown.
- Understanding these mechanisms is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the function of a novel circRNA, circ-0001283, in myocardial hypertrophy.
- To elucidate the molecular mechanisms by which circ-0001283 influences cardiac hypertrophy progression.
- To evaluate circ-0001283 as a potential therapeutic target for cardiac hypertrophy.
Main Methods:
- Identified and characterized circ-0001283 expression in cardiac hypertrophy models.
- Investigated the interaction between circ-0001283 and myosin light chain 3 (MYL3).
- Utilized knockdown and overexpression techniques to assess functional impacts.
- Analyzed downstream signaling pathways including autophagy, PI3K/Akt/mTOR, and ERK.
Main Results:
- Circ-0001283 directly interacts with MYL3, inhibiting its ubiquitination and enhancing protein expression.
- Knockdown of circ-0001283 reduced cardiac hypertrophy, an effect reversed by MYL3 overexpression.
- MYL3 promotes hypertrophy by inducing autophagy via the PI3K/Akt/mTOR and ERK signaling pathways.
Conclusions:
- Circ-0001283 up-regulates MYL3 expression, which in turn promotes autophagy and accelerates cardiac hypertrophy.
- The mechanism involves direct interaction and inhibition of ubiquitination, not a competing endogenous RNA pathway.
- Circ-0001283 emerges as a promising therapeutic target for managing cardiac hypertrophy.
Abstract:
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.
