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Aberrant expression of miR-29b-3p influences heart development and cardiomyocyte proliferation by targeting NOTCH2.


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.

SUBMITTER: Yang Q 

PROVIDER: S-EPMC7106969 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Aberrant expression of miR-29b-3p influences heart development and cardiomyocyte proliferation by targeting NOTCH2.

Yang Qian Q   Wu Fang F   Mi Yaping Y   Wang Feng F   Cai Ke K   Yang Xiaoshan X   Zhang Ranran R   Liu Lian L   Zhang Yawen Y   Wang Youhua Y   Wang Xu X   Xu Mingqing M   Gui Yonghao Y   Li Qiang Q  

Cell proliferation 20200220 3


<h4>Objectives</h4>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.<h4>Materials and methods</h4>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 t  ...[more]

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