miR-731 modulates the zebrafish heart morphogenesis via targeting Calcineurin/Nfatc3a pathway

Zebrafish miR-731 is orthologous of human miR-425, which has been demonstrated to have cardio-protective roles by a variety of mechanisms. The miR-731 morphants show pericardium enlargement, and many DEGs (differentially expressed genes) are enriched in ‘Cardiac muscle contraction’ and ‘Calcium sign...

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Published in:Biochimica et biophysica acta. General subjects Vol. 1866; no. 6; p. 130133
Main Authors: Huang, Yan, Wang, Wei-Feng, Huang, Chun-Xiao, Li, Xuan-Hui, Liu, Hong, Wang, Huan-Ling
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01.06.2022
Subjects:
Animals
Calcineurin - genetics
Calcineurin - metabolism
Calcineurin/Nfatc3a
calcium
cardiac output
Danio rerio
Development
gene expression
gene expression regulation
genes
Heart
heart rate
humans
hybridization
luciferase
MicroRNAs - genetics
MicroRNAs - metabolism
miR-731
morphogenesis
Morphogenesis - genetics
muscle contraction
myocardium
pericardium
sequence analysis
Western blotting
Zebrafish
Zebrafish - genetics
Zebrafish - metabolism
Zebrafish Proteins - genetics
Heart
Development
Calcineurin/Nfatc3a
Zebrafish
miR-731
ISSN:0304-4165, 1872-8006, 1872-8006
Online Access:Get full text
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Summary:Zebrafish miR-731 is orthologous of human miR-425, which has been demonstrated to have cardio-protective roles by a variety of mechanisms. The miR-731 morphants show pericardium enlargement, and many DEGs (differentially expressed genes) are enriched in ‘Cardiac muscle contraction’ and ‘Calcium signaling pathway’, implying that miR-731 plays a potential role in heart function and development. However，the in vivo physiological role of miR-731 in the heart needs to be fully defined. Zebrafish miR-731 morphants were generated by morpholino knockdown, and miR-731 knockout zebrafish was generated by CRISRP/Cas9. We observed cardiac morphogenesis based on whole-mount in situ hybridization. Furthermore, RNA-seq and qRT-PCR were used to elucidate the molecular mechanism and analyze the gene expression. Double luciferase verification and Western blot were used to verify the target gene. The depletion of miR-731 in zebrafish embryos caused the deficiency of cardiac development and function, which was associated with reduced heart rate, ventricular enlargement and heart looping disorder. In addition, mechanistic study demonstrated that Calcineurin/Nfatc3a signaling involved in miR-731 depletion induced abnormal cardiac function and developmental defects. MiR-731 regulates cardiac function and morphogenesis through Calcineurin/Nfatc3a signaling. Our studies highlight the potential importance of miR-731 in cardiac development. •Zebrafish miR-731−/− knockout mutant was generated.•nfatc3a is a direct target of miR-731.•Calcineurin/Nfatc3a signaling is involved in miR-731 depletion induced heart morphogenesis.
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ISSN:0304-4165
1872-8006
1872-8006
DOI:10.1016/j.bbagen.2022.130133