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

• Published in: Gene therapy 2021-12, Vol.28 (12), p.718-728
• Main Authors: Fang, Yan, Tao, Yu, Zhou, Haiwen, Lai, Hengli
• Format: Article
• Language: English
• Subjects: 13/109; 42/109; 631/337; 631/80; Biomedical and Life Sciences; Biomedicine; Cardiomegaly - genetics; Cardiomegaly - metabolism; Cardiomyocytes; CELF1 Protein - metabolism; Cell Biology; Cellular signal transduction; Development and progression; Gene Expression; Gene Therapy; Genetic aspects; Health aspects; Heart enlargement; Human Genetics; Humans; Hypertrophy; Immunofluorescence; MicroRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Myocytes, Cardiac - metabolism; Nanotechnology; Neonates; Phenotypes; Polycomb Repressive Complex 2 - metabolism; Transcription factors
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/s41434-020-0165-5

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.