Back to Search Start Over

Circular RNA circRNA_000203 aggravates cardiac hypertrophy via suppressing miR-26b-5p and miR-140-3p binding to Gata4

Authors :
Sheng Wang
Jing Yang
Jin-Dong Xu
Hui Li
Ni Zeng
Xi-Pei Wang
Zhi-Xin Shan
Hui Yang
Shujing Yuan
Jian-Fang Luo
Xian-Hong Fang
Shulin Wu
Jin-Zhu Duan
Rong Pan
Jie-Ning Zhu
Zhen-Zhen Yang
Source :
Cardiovascular Research
Publication Year :
2019
Publisher :
Oxford University Press, 2019.

Abstract

Aims Circular RNAs (circRNAs) are involved in gene regulation in a variety of physiological and pathological processes. The present study aimed to investigate the effect of circRNA_000203 on cardiac hypertrophy and the potential mechanisms involved. Methods and results CircRNA_000203 was found to be up-regulated in the myocardium of Ang-II-infused mice and in the cytoplasma of Ang-II-treated neonatal mouse ventricular cardiomyocytes (NMVCs). Enforced expression of circRNA_000203 enhances cell size and expression of atrial natriuretic peptide and β-myosin heavy chain in NMVCs. In vivo, heart function was impaired and cardiac hypertrophy was aggravated in Ang-II-infused myocardium-specific circRNA_000203 transgenic mice (Tg-circ203). Mechanistically, we found that circRNA_000203 could specifically sponge miR-26b-5p, -140-3p in NMVCs. Further, dual-luciferase reporter assay showed that miR-26b-5p, -140-3p could interact with 3′-UTRs of Gata4 gene, and circRNA_000203 could block the above interactions. In addition, Gata4 expression is transcriptionally inhibited by miR-26b-5p, -140-3p mimic in NMVCs but enhanced by over-expression of circRNA_000203 in vitro and in vivo. Functionally, miR-26b-5p, -140-3p, and Gata4 siRNA, could reverse the hypertrophic growth in Ang-II-induced NMVCs, as well as eliminate the pro-hypertrophic effect of circRNA_000203 in NMVCs. Furthermore, we demonstrated that NF-κB signalling mediates the up-regulation of circRNA_000203 in NMVCs exposed to Ang-II treatment. Conclusions Our data demonstrated that circRNA_000203 exacerbates cardiac hypertrophy via suppressing miR-26b-5p and miR-140-3p leading to enhanced Gata4 levels.<br />Graphical Abstract Graphical Abstract

Details

Language :
English
ISSN :
17553245 and 00086363
Volume :
116
Issue :
7
Database :
OpenAIRE
Journal :
Cardiovascular Research
Accession number :
edsair.doi.dedup.....5ddcfd9273f72d5260bf2aeb7624947c