Overexpression of miR-19b impairs cardiac development in zebrafish by targeting ctnnb1

Mengmeng Li, Xiaoshan Hu, Jingai Zhu, Chun Zhu, Shasha Zhu, Xuehua Liu, Jing Xu, Shuping Han, Zhangbin Yu

Research output: Contribution to journalArticlepeer-review

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 GSK3β inhibitor lithium chloride. Conclusion: Our findings suggest that miR-19b regulates laterality development and heart looping in zebrafish embryos by targeting ctnnb1.

Original languageEnglish (US)
Pages (from-to)1988-2002
Number of pages15
JournalCellular Physiology and Biochemistry
Volume33
Issue number6
DOIs
StatePublished - Jul 2014
Externally publishedYes

Keywords

  • Cardiac development
  • Zebrafish
  • ctnnb1
  • miR-19b

ASJC Scopus subject areas

  • Physiology

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