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首页> 外文期刊>Protoplasma: An International Journal of Cell Biology >MicroRNA-375 overexpression disrupts cardiac development of Zebrafish (Danio rerio) by targetingnotch2
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MicroRNA-375 overexpression disrupts cardiac development of Zebrafish (Danio rerio) by targetingnotch2

机译：MicroRNA-375过度表达扰乱了TargetNotch2的斑马鱼（Danio Rerio）的心脏发育

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摘要

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 mu M) 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 confirmednotch2, 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 targetingnotch2, indicating its potential as a diagnostic marker.
机译：MicroRNA是小型非编码RNA，对于适当的心脏发育很重要。在我们以前的胎儿进行心室间隔缺陷的研究中，我们发现MicroRNA-375（miR-375）明显上调，与健康对照相比。我们的研究还证实，MIR-375对心肌细胞分化至关重要。本研究主要集中在使用斑马鱼模型的MiR-375的生物学意义和机制。我们用1-2NL的miR-375注射斑马鱼胚胎，以各种浓度（0/2/4/8 mu m）或阴性对照。单独评估变形和死亡率。通过QRT-PCR检测MiR-375和相关基因的不同表达水平，并使用荧光素酶测定和原位杂交来阐明胚胎发育期间miR-375的机制。 miR-375的过度表达扰乱了斑马鱼胚胎的心脏发育。 MiR-375的破坏导致心率下降，心包水肿和心脏异常异常。由于miR-375的过度表达，涉及心脏发育的各种基因。此外，陷波信号传导途径受到影响，并且荧光素酶报告基因分析确认Notch2，其被生物信息学分析预测为miR-375的靶基因。我们的研究结果表明，miR-375的过表达对胚胎发育有害，包括心脏发育，并且可以部分模拟多系统疾病。 miR-375在靶向Notch2的斑马鱼胚胎心脏形态发生期间具有重要作用，表明其作为诊断标记的潜力。

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  • 作者

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

  • 作者单位

    Nanjing Med Univ Nanjing Matern &

    Child Hlth Care Hosp Dept Child Hlth Care Womens Hosp 123rd Tianfei St Mochou Rd Nanjing 210004 Peoples R China;

    Shanghai Jiao Tong Univ Tongren Hosp Dept Pediat Sch Med 1111 XianXia Rd Shanghai 200336 Peoples R China;

    Nanjing Med Univ Nanjing Matern &

    Child Hlth Care Hosp Dept Child Hlth Care Womens Hosp 123rd Tianfei St Mochou Rd Nanjing 210004 Peoples R China;

    Nanjing Med Univ Nanjing Matern &

    Child Hlth Care Hosp Dept Pediat Womens Hosp 123rd Tianfei St Mochou Rd Nanjing 210004 Peoples R China;

    Nanjing Med Univ Nanjing Matern &

    Child Hlth Care Hosp Dept Pediat Womens Hosp 123rd Tianfei St Mochou Rd Nanjing 210004 Peoples R China;

    Nanjing Med Univ Nanjing Matern &

    Child Hlth Care Hosp Dept Pediat Womens Hosp 123rd Tianfei St Mochou Rd Nanjing 210004 Peoples R China;

    Nanjing Med Univ Nanjing Matern &

    Child Hlth Care Hosp Dept Child Hlth Care Womens Hosp 123rd Tianfei St Mochou Rd Nanjing 210004 Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞形态学;
  • 关键词

    miR-375; Cardiac development; Overexpression; notch2;

    机译：miR-375;心脏发育;过表达;Notch2;

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