MicroRNA-375 overexpression disrupts cardiac development of Zebrafish ( Danio rerio ) by targeting notch2
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ORIGINAL ARTICLE
MicroRNA-375 overexpression disrupts cardiac development of Zebrafish (Danio rerio) by targeting notch2 Sisi Zhuang 1,2 & Yanrong Fu 4 & Jingyun Li 1 & Mengmeng Li 3 & Xiaoshan Hu 3 & Jingai Zhu 3 & Meiling Tong 1 Received: 24 October 2019 / Accepted: 13 February 2020 # Springer-Verlag GmbH Austria, part of Springer Nature 2020
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 miR375 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. Keywords miR-375 . Cardiac development . Overexpression . notch2 Sisi Zhuang and Yanrong Fu contributed equally to this work. Handling Editor: Reimer Stick Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00709-020-01490-4) contains supplementary material, which is available to authorized users. * Jingai Zhu [email protected] * Meiling Tong [email protected] 1
Department of Child Health Care, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, 123rd Tianfei Street, Mochou Road, Nanjing 210004, China
2
Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Jiangsu Province, Nanjing 210029, China
3
Department of Pediatrics, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, 123rd Tianfei Street, Mochou Road, Nanjing 210004, China
4
Department of Pediatrics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 XianXia Road, Shanghai 20
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