MicroRNA-375 overexpression disrupts cardiac development of Zebrafish (Danio rerio) by targeting notch2

Sisi Zhuang, Yanrong Fu, Jingyun Li, Mengmeng Li, Xiaoshan Hu, Jingai Zhu, Meiling Tong

Research output: Contribution to journalArticlepeer-review

Abstract

MicroRNAs are small noncoding RNAs that are important for proper cardiac development. In our previous study of fetuses with ventricular septal defects, we discovered that microRNA-375 (miR-375) is obviously upregulated compared with that in healthy controls. Our study also confirmed that miR-375 is crucial for cardiomyocyte differentiation. This research mainly focused on the biological significance and mechanism of miR-375 using a zebrafish model. We injected zebrafish embryos with 1–2 nl of a miR-375 mimic at various concentrations (0/2/4/8 μM) or with negative control. The deformation and mortality rates were separately assessed. The different expression levels of miR-375 and related genes were examined by qRT-PCR, and luciferase assays and in situ hybridization were used to clarify the mechanism of miR-375 during embryonic development. Overexpression of miR-375 disrupted the cardiac development of zebrafish embryos. Disruption of miR-375 led to a decreased heart rate, pericardial edema, and abnormal cardiac looping. Various genes involved in cardiac development were downregulated due to the overexpression of miR-375. Moreover, the NOTCH signaling pathway was affected, and the luciferase reporter gene assays confirmed notch2, which was predicted by bioinformatics analysis, as the target gene of miR-375. Our findings demonstrated that the overexpression of miR-375 is detrimental to embryonic development, including cardiac development, and can partially simulate a multisystemic disorder. MiR-375 has an important role during cardiac morphogenesis of zebrafish embryos by targeting notch2, indicating its potential as a diagnostic marker.

Original languageEnglish (US)
Pages (from-to)1309-1318
Number of pages10
JournalProtoplasma
Volume257
Issue number5
DOIs
StatePublished - Sep 1 2020
Externally publishedYes

Keywords

  • Cardiac development
  • Overexpression
  • miR-375
  • notch2

ASJC Scopus subject areas

  • Plant Science
  • Cell Biology

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