Serum miR-206 and other muscle-specific microRNAs as non-invasive biomarkers for Duchenne muscular dystrophy

Authors

  • Jun Hu,

    1. Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
    2. Key Laboratory of Pediatrics in Chongqing, Chongqing, China
    3. Chongqing International Science, Technology Cooperations Center for Child Development and Disorders, Chongqing, China
    4. Department of Neurology, Children's Hospital, Chongqing Medical University, Chongqing, China
    5. Department of Pediatrics, Union Hospital, Fujian Medical University, Fuzhou, China
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  • Min Kong,

    1. Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
    2. Key Laboratory of Pediatrics in Chongqing, Chongqing, China
    3. Chongqing International Science, Technology Cooperations Center for Child Development and Disorders, Chongqing, China
    4. Department of Neurology, Children's Hospital, Chongqing Medical University, Chongqing, China
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  • Yuanzhen Ye,

    1. Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
    2. Key Laboratory of Pediatrics in Chongqing, Chongqing, China
    3. Chongqing International Science, Technology Cooperations Center for Child Development and Disorders, Chongqing, China
    4. Department of Neurology, Children's Hospital, Chongqing Medical University, Chongqing, China
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  • Siqi Hong,

    1. Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
    2. Key Laboratory of Pediatrics in Chongqing, Chongqing, China
    3. Chongqing International Science, Technology Cooperations Center for Child Development and Disorders, Chongqing, China
    4. Department of Neurology, Children's Hospital, Chongqing Medical University, Chongqing, China
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  • Li Cheng,

    1. Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
    2. Key Laboratory of Pediatrics in Chongqing, Chongqing, China
    3. Chongqing International Science, Technology Cooperations Center for Child Development and Disorders, Chongqing, China
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  • Li Jiang

    Corresponding author
    1. Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
    2. Key Laboratory of Pediatrics in Chongqing, Chongqing, China
    3. Chongqing International Science, Technology Cooperations Center for Child Development and Disorders, Chongqing, China
    4. Department of Neurology, Children's Hospital, Chongqing Medical University, Chongqing, China
    • Address correspondence and reprint requests to Li Jiang, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China. E-mail: dr.jiangl@hotmail.com

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Abstract

Creatine kinase has been utilized as a diagnostic marker for Duchenne muscular dystrophy (DMD), but it correlates less well with the DMD pathological progression. In this study, we hypothesized that muscle-specific microRNAs (miR-1, -133, and -206) in serum may be useful for monitoring the DMD pathological progression, and explored the possibility of these miRNAs as potential non-invasive biomarkers for the disease. By using real-time quantitative reverse transcription–polymerase chain reaction in a randomized and controlled trial, we detected that miR-1, -133, and -206 were significantly over-expressed in the serum of 39 children with DMD (up to 3.20 ± 1.20, 2−ΔΔCt): almost 2- to 4-fold enriched in comparison to samples from the healthy controls (less than 1.15 ± 0.34, 2−ΔΔCt). To determine whether these miRNAs were related to the clinical features of children with DMD, we analyzed the associations compared to creatine kinase. There were very good inverse correlations between the levels of these miRNAs, especially miR-206, and functional performances: high levels corresponded to low muscle strength, muscle function, and quality of life. Moreover, by receiver operating characteristic curves analyses, we revealed that these miRNAs, especially miR-206, were able to discriminate DMD from controls. Thus, miR-206 and other muscle-specific miRNAs in serum are useful for monitoring the DMD pathological progression, and hence as potential non-invasive biomarkers for the disease.

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There has been a long-standing need for reliable, non-invasive biomarkers for Duchenne muscular dystrophy (DMD). We found that the levels of muscle-specific microRNAs, especially miR-206, in the serum of DMD were 2- to 4-fold higher than in the controls. High levels corresponded to low muscle strength, muscle function, and quality of life (QoL). These miRNAs were able to discriminate DMD from controls by receiver operating characteristic (ROC) curves analyses. Thus, miR-206 and other muscle-specific miRNAs are useful as non-invasive biomarkers for DMD.

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