Silencing of circCacna1c Inhibits ISO-Induced Cardiac Hypertrophy through miR-29b-2-5p/NFATc1 Axis
Peilei Lu, Danyu Zhang, Fan Ding, Jialu Ma, Yang K. Xiang, Meimi Zhao
Abstract
Pathological cardiac hypertrophy is one of the notable causes of heart failure. Circular RNAs (circRNAs) have been studied in association with cardiac hypertrophy; however, the mechanisms by which circRNAs regulate cardiac hypertrophy remain unclear. In this study, we identified a new circRNA, named circCacna1c, in cardiac hypertrophy. Adult male C57BL/6 mice and H9c2 cells were treated with isoprenaline hydrochloride (ISO) to establish a hypertrophy model. We found that circCacna1c was upregulated in ISO-induced hypertrophic heart tissue and H9c2 cells. Western blot and quantitative real-time polymerase chain reaction showed that silencing circCacna1c inhibited hypertrophic gene expression in ISO-induced H9c2 cells. Mechanistically, circCacna1c competitively bound to miR-29b-2-5p in a dual-luciferase reporter assay, which was downregulated in ISO-induced hypertrophic heart tissue and H9c2 cells. MiR-29b-2-5p inhibited the nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) to control hypertrophic gene expression. After silencing circCacna1c, the expression of miR-29b-2-5p increased, which reduced hypertrophic gene expression by inhibiting NFATc1 expression. Together, these experiments indicate that circCacna1c promotes ISO-induced pathological hypertrophy through the miR-29b-2-5p/NFATc1 axis.