PUBLICATION
Aberrant expression of miR-29b-3p influences heart development and cardiomyocyte proliferation by targeting NOTCH2
- Authors
- Yang, Q., Wu, F., Mi, Y., Wang, F., Cai, K., Yang, X., Zhang, R., Liu, L., Zhang, Y., Wang, Y., Wang, X., Xu, M., Gui, Y., Li, Q.
- ID
- ZDB-PUB-200222-6
- Date
- 2020
- Source
- Cell Proliferation 53(3): e12764 (Journal)
- Registered Authors
- Wang, Fang, Wang, Xu, Wang, Youhua
- Keywords
- NOTCH2, congenital heart disease, microRNA-29b-3p, proliferation
- MeSH Terms
-
- Animals
- Cell Proliferation
- Cells, Cultured
- Child, Preschool
- Down-Regulation
- Female
- Heart/embryology
- Heart Defects, Congenital/genetics*
- Heart Defects, Congenital/pathology
- Humans
- Infant
- Male
- Mice
- MicroRNAs/genetics*
- Myocytes, Cardiac/cytology
- Myocytes, Cardiac/metabolism
- Myocytes, Cardiac/pathology*
- Receptor, Notch2/genetics*
- Up-Regulation
- Zebrafish
- PubMed
- 32077168 Full text @ Cell Prolif.
Citation
Yang, Q., Wu, F., Mi, Y., Wang, F., Cai, K., Yang, X., Zhang, R., Liu, L., Zhang, Y., Wang, Y., Wang, X., Xu, M., Gui, Y., Li, Q. (2020) Aberrant expression of miR-29b-3p influences heart development and cardiomyocyte proliferation by targeting NOTCH2. Cell Proliferation. 53(3):e12764.
Abstract
Objectives microRNA-29 (miR-29) family have shown different expression patterns in cardiovascular diseases. Our study aims to explore the effect and mechanism of miR-29 family on cardiac development.
Materials and methods A total of 13 patients with congenital heart disease (CHD) and 7 controls were included in our study. Tissues were obtained from the right ventricular outflow tract (RVOT) after surgical resection or autopsy. The next-generation sequencing was applied to screen the microRNA expression profiles of CHD. Quantitative RT-PCR and Western blot were employed to measure genes expression. Tg Cmlc2: GFP reporter zebrafish embryos were injected with microRNA (miRNA) to explore its role in cardiac development in vivo. Dual-luciferase reporter assay was designed to validate the target gene of miRNAs. CCK-8 and EdU incorporation assays were performed to evaluate cardiomyocyte proliferation.
Results Our study showed miR-29b-3p expression was significantly increased in the RVOT of the CHD patients. Injection of miR-29b-3p into zebrafish embryos induced higher mortality and malformation rates, developmental delay, cardiac malformation and dysfunction. miR-29b-3p inhibited cardiomyocyte proliferation, and its inhibitor promoted cardiomyocyte proliferation in vitro and in vivo. Furthermore, we identified that miR-29b-3p influenced cardiomyocyte proliferation by targeting NOTCH2, which was down-regulated in the RVOT of the CHD patients.
Conclusion This study reveals that miR-29b-3p functions as a novel regulator of cardiac development and inhibits cardiomyocyte proliferation via NOTCH2, which provides novel insights into the aetiology and potential treatment of CHD.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping