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Promoting role of circ-Jarid2/miR-129-5p/Celf1 axis in cardiac hypertrophy

Gene Therapy volume 28, pages 718–728 (2021)Cite this article

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Abstract

Cardiac hypertrophy is imposed much pressure on heart and threatening our live. Previous study suggested that dysregulation of Celf1 is largely connecting to neonatal cardiac dysfunction. Hence, we aimed to explore the precise function and probable regulatory mechanism upstream of Celf1in cardiac hypertrophy. Here, Ang-II treatment was implemented to stimulate hypertrophic phenotypes inH9C2 and MCM cells. Immunofluorescence assay was conducted to measure the surface area of cardiomyocytes. And qRT-PCR assay was conducted to investigate gene expression. Moreover, western blot assay was conducted to probe the protein levels. Results uncovered that Celf1 expression was increased dependent on elevated Ang-II concentration, and that inhibited Celf1 could relieve the Ang-II-caused cardiac hypertrophy. Significantly, Celf1was found to be targeted by miR-129-5p but then released via the sponging role of circ-Jarid2. Furthermore, circ-Jarid2 was found to promote cardiac hypertrophy, whereas miR-129-5p played suppressing parts in hypertrophic cardiomyocytes. Moreover, we verified circ-Jarid2 contributed to cardiac hypertrophy via miR-129-5p/Celf1 axis both in vitro and in vivo. In conclusion, circ-Jarid2/miR-129-5p/Celf1 axis aggravates cardiac hypertrophy, which provides new ideas for developing treatment strategies for patients with cardiac hypertrophy.

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Fig. 1: Silencing Celf1 could relieve Ang-II-induced cardiac hypertrophy.
Fig. 2: MiR-129-5p could bind to Celf1 and circ-Jarid2.
Fig. 3: Circ-Jarid2 functioned in cardiac hypertrophy.
Fig. 4: MiR-129-5p could relieve the response of cardiac hypertrophy.
Fig. 5: Circ-Jarid2/miR-129-5p/Celf1 axis modulated the hypertrophic response of rat and mouse cardiomyocyte.
Fig. 6: Impact of circ-Jarid2/miR-129-5p/Celf1 axis in vivo.

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Acknowledgements

We appreciate the experimenters.

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  1. Department of Cardiology, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang, 330006, Jiangxi, China

    Yan Fang, Yu Tao, Haiwen Zhou & Hengli Lai

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  1. Yan Fang
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Fang, Y., Tao, Y., Zhou, H. et al. Promoting role of circ-Jarid2/miR-129-5p/Celf1 axis in cardiac hypertrophy. Gene Ther 28, 718–728 (2021). https://doi.org/10.1038/s41434-020-0165-5

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