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Updated: Jul 6, 2025
In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge
Published on: June 15, 2018
Circular RNA-circPan3 attenuates cardiac hypertrophy via miR-320-3p/HSP20 axis
Xinyu Fang1, Xiang Ao1, Dandan Xiao1
1School of Basic Medicine, Qingdao University, Qingdao, 266071, China.
Insights
Circular RNA circPan3 protects against cardiac hypertrophy by regulating the miR-320-3p/HSP20 pathway. Its expression is decreased by isoproterenol via ALKBH5-mediated methylation, offering potential therapeutic targets for heart disease.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Epigenetics
Background:
- Circular RNAs (circRNAs) are prevalent in cardiac tissue and implicated in heart disease pathogenesis.
- circPan3, a conserved heart-enriched circRNA, is investigated for its role in cardiac hypertrophy.
Purpose of the Study:
- To elucidate the regulatory mechanism of circPan3 in cardiac hypertrophy.
- To determine the therapeutic potential of circPan3 in heart disease.
Main Methods:
- Cardiac hypertrophy induced by isoproterenol in a mouse model.
- Assessment of cardiomyocyte hypertrophy via cell surface area and marker expression.
- RNA pull-down assays and methylated RNA immunoprecipitation to analyze molecular interactions and N6-methylation (m6A).
Main Results:
- circPan3 expression decreased in isoproterenol-induced cardiac hypertrophy.
- Overexpression of circPan3 attenuated hypertrophy; inhibition aggravated it.
- circPan3 acts as a sponge for miR-320-3p, upregulating HSP20. Isoproterenol reduced ALKBH5, leading to circPan3 destabilization via m6A.
Conclusions:
- circPan3 exhibits an antihypertrophic effect in cardiomyocytes.
- A novel circPan3-miR-320-3p-HSP20 pathway regulated by ALKBH5-mediated m6A is identified in cardiac hypertrophy.
- This pathway presents potential therapeutic targets for cardiac hypertrophy.
Background:
Circular RNAs are enriched in cardiac tissue and play important roles in the pathogenesis of heart diseases. In this study, we aimed to investigate the regulatory mechanism of a conserved heart-enriched circRNA, circPan3, in cardiac hypertrophy.
Methods:
Cardiac hypertrophy was induced by isoproterenol. The progression of cardiomyocyte hypertrophy was assessed by sarcomere organization staining, cell surface area measurement, and expression levels of cardiac hypertrophy markers. RNA interactions were detected by RNA pull-down assays, and methylated RNA immunoprecipitation was used to detect m6A level.
Results:
The expression of circPan3 was downregulated in an isoproterenol-induced cardiac hypertrophy model. Forced expression of circPan3 attenuated cardiomyocyte hypertrophy, while inhibition of circPan3 aggravated cardiomyocyte hypertrophy. Mechanistically, circPan3 was an endogenous sponge of miR-320-3p without affecting miR-320-3p levels. It elevated the expression of HSP20 by endogenously interacting with miR-320-3p. In addition, circPan3 was N6-methylated. Stimulation by isoproterenol downregulated the m6A eraser ALKBH5, resulting in N6-methylation and destabilization of circPan3.
Conclusions:
Our research is the first to report that circPan3 has an antihypertrophic effect in cardiomyocytes and revealed a novel circPan3-modulated signalling pathway involved in cardiac hypertrophy. CircPan3 inhibits cardiac hypertrophy by targeting the miR-320-3p/HSP20 axis and is regulated by ALKBH5-mediated N6-methylation. This pathway could provide potential therapeutic targets for cardiac hypertrophy.
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