Circular RNA-circPan3 attenuates cardiac hypertrophy via miR-320-3p/HSP20 axis

• Published in: Cellular & Molecular Biology Letters
• Main Authors: Xinyu Fang, Xiang Ao, Dandan Xiao, Yu Wang, Yi Jia, Peiyan Wang, Mengyang Li, Jianxun Wang
• Format: Article
• Language: English
• Published: BMC 2024-01-01
• Subjects: Cardiac hypertrophy; m6A modification; Circular RNA; circPan3; miR-320-3p; HSP20
• Online Access: https://doi.org/10.1186/s11658-023-00520-2

Abstract 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. Graphical Abstract