miRNA-940 reduction contributes to human Tetralogy of Fallot development

Authors

  • Dandan Liang,

    1. Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China
    2. Institute of Medical Genetics, Tongji University, Shanghai, China
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    • These authors contributed equally to this work.
  • Xinran Xu,

    1. Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China
    2. Institute of Medical Genetics, Tongji University, Shanghai, China
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    • These authors contributed equally to this work.
  • Fangfei Deng,

    1. Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China
    2. Institute of Medical Genetics, Tongji University, Shanghai, China
    3. Department of Cardiology, East Hospital, Tongji University, Shanghai, China
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    • These authors contributed equally to this work.
  • Jing Feng,

    1. Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China
    2. Institute of Medical Genetics, Tongji University, Shanghai, China
    3. Department of Cardiology, East Hospital, Tongji University, Shanghai, China
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    • These authors contributed equally to this work.
  • Hong Zhang,

    1. Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China
    2. Institute of Medical Genetics, Tongji University, Shanghai, China
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  • Ying Liu,

    1. Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China
    2. Institute of Medical Genetics, Tongji University, Shanghai, China
    3. Department of Cardiology, East Hospital, Tongji University, Shanghai, China
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  • Yangyang Zhang,

    1. Cardiothoracic Surgical Department, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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  • Lei Pan,

    1. Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China
    2. Institute of Medical Genetics, Tongji University, Shanghai, China
    3. Department of Cardiology, East Hospital, Tongji University, Shanghai, China
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  • Yi Liu,

    1. Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China
    2. Institute of Medical Genetics, Tongji University, Shanghai, China
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  • Dasheng Zhang,

    1. Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China
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  • Jun Li,

    1. Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China
    2. Institute of Medical Genetics, Tongji University, Shanghai, China
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  • Xingqun Liang,

    1. Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China
    2. Institute of Medical Genetics, Tongji University, Shanghai, China
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  • Yunfu Sun,

    1. Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China
    2. Institute of Medical Genetics, Tongji University, Shanghai, China
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  • Junjie Xiao,

    1. Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China
    2. Institute of Medical Genetics, Tongji University, Shanghai, China
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  • Yi-Han Chen

    Corresponding author
    1. Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China
    2. Institute of Medical Genetics, Tongji University, Shanghai, China
    3. Department of Cardiology, East Hospital, Tongji University, Shanghai, China
    4. Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai, China
    • Correspondence to: Yi-Han CHEN, Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, East Hospital,Tongji University School of Medicine,

      Tel.: +086-21-58766224

      Fax: +086-21-65989086

      E-mail: yihanchen@tongji.edu.cn

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Abstract

Tetralogy of Fallot (TOF) is a complex congenital heart defect and the microRNAs regulation in TOF development is largely unknown. Herein, we explored the role of miRNAs in TOF. Among 75 dysregulated miRNAs identified from human heart tissues, miRNA-940 was the most down-regulated one. Interestingly, miRNA-940 was most highly expressed in normal human right ventricular out-flow tract comparing to other heart chambers. As TOF is caused by altered proliferation, migration and/or differentiation of the progenitor cells of the secondary heart field, we isolated Sca-1+ human cardiomyocyte progenitor cells (hCMPC) for miRNA-940 function analysis. miRNA-940 reduction significantly promoted hCMPCs proliferation and inhibited hCMPCs migration. We found that JARID2 is an endogenous target regulated by miRNA-940. Functional analyses showed that JARID2 also affected hCMPCs proliferation and migration. Thus, decreased miRNA-940 affects the proliferation and migration of the progenitor cells of the secondary heart field by targeting JARID2 and potentially leads to TOF development.

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