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

Cardiovasc Res. 2020 Jun 1;116(7):1323-1334. doi: 10.1093/cvr/cvz215.


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.

Keywords: Cardiac hypertrophy; CircRNA_000203; Circular RNA; MicroRNA-140-3p; MicroRNA-26b-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Binding Sites
  • Cells, Cultured
  • Disease Models, Animal
  • Female
  • GATA4 Transcription Factor / genetics
  • GATA4 Transcription Factor / metabolism*
  • Gene Expression Regulation
  • Humans
  • Hypertrophy, Left Ventricular / genetics
  • Hypertrophy, Left Ventricular / metabolism*
  • Hypertrophy, Left Ventricular / pathology
  • Hypertrophy, Left Ventricular / physiopathology
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Signal Transduction
  • Ventricular Function, Left*
  • Ventricular Remodeling*


  • 3' Untranslated Regions
  • GATA4 Transcription Factor
  • Gata4 protein, mouse
  • MIRN140 microRNA, mouse
  • MicroRNAs
  • Mirn26 microRNA, mouse
  • RNA, Circular