Overexpression of miR-19b impairs cardiac development in zebrafish by targeting ctnnb1.
Cell Physiol Biochem
; 33(6): 1988-2002, 2014.
Article
em En
| MEDLINE
| ID: mdl-25034767
ABSTRACT
BACKGROUND:
MicroRNAs are broadly accepted as crucial regulators of cardiovascular development, and dysregulation of their expression has been linked to cardiac disease. MicroRNA cluster miR-17-92 has been implicated in cardiac development and function, yet its defined mechanisms of action in this context are uncertain. Here, we focused on miR-19b, a key component of the miR-17-92 cluster proven to induce cardiomyocyte proliferation in vitro. We aimed to identify the biological significance of miR-19b in cardiac development and its underlying molecular mechanism of action in vivo.METHODS:
We micro-injected zebrafish embryos with different concentrations (0, 2, 4 and 8 µm) of miR-19b mimics or a negative control, and assessed the embryo malformation rate, mortality rate, hatching rate and heart abnormalities at 72 hours post-fertilization (72 hpf).RESULTS:
We found that overexpression of miR-19b impacted left-right symmetry and cardiac development of zebrafish embryos, characterized by pericardial edema, slower heart rate and cardiac looping defects in a dose-dependent manner. Moreover, several important signaling molecules in the Wnt signaling pathway were abnormally expressed, suggesting that overexpression of miR-19b induces the inhibition of the Wnt signaling pathway by directly targeting ctnnb1. Interestingly, the deformed cardiac phenotype was partially rescued by treatment with the GSK3ß inhibitor lithium chloride.CONCLUSION:
Our findings suggest that miR-19b regulates laterality development and heart looping in zebrafish embryos by targeting ctnnb1.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peixe-Zebra
/
Proteínas de Peixe-Zebra
/
MicroRNAs
/
Beta Catenina
/
Miocárdio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article