• Open Access

miRNAS in normal and diseased skeletal muscle

Authors

  • Iris Eisenberg,

    1. Howard Hughes Medical Institute, Childrens Hospital Boston, Boston, MA, USA
    2. Program in Genomics, Division of Genetics, Children's Hospital Boston and Department of Genetics, Harvard Medical School, Boston, MA, USA
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      These authors contributed equally to this manuscript.

  • Matthew S. Alexander,

    1. Program in Genomics, Division of Genetics, Children's Hospital Boston and Department of Genetics, Harvard Medical School, Boston, MA, USA
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      These authors contributed equally to this manuscript.

  • Louis M. Kunkel

    Corresponding author
    1. Howard Hughes Medical Institute, Childrens Hospital Boston, Boston, MA, USA
    2. Program in Genomics, Division of Genetics, Children's Hospital Boston and Department of Genetics, Harvard Medical School, Boston, MA, USA
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Correspondence to: Louis M. KUNKEL, Ph.D., Children's Hospital Boston, 300 Longwood Ave., Boston, MA 02115, USA.
Tel.: 617.355.7576
Fax: 617.730.0253
E-mail: kunkel@enders.tch.harvard.edu

Abstract

  • • Introduction
  • • Mechanisms of miRNA-mediated repression
  • • miRNA regulatory network in muscle
    • - Muscle-specific miRNAs
    • - Non-muscle-specific miRNAs
  • • miRNA signatures as biomarkers of myopathies
  • • miRNA therapeutic promise
    • - Locked nucleic acids (LNAs) and antagomiRs
    • - Overexpression of miRNAs in myopathies
    • - Specificity of miRNA treatment
    • - miRNAs as regulators of myogenic stem cells
  • • Perspective

Abstract

The last 20 years have witnessed major advances in the understanding of muscle diseases and significant inroads are being made to treat muscular dystrophy. However, no curative therapy is currently available for any of the muscular dystrophies, despite the immense progress made using several approaches and only palliative and symptomatic treatment is available for patients. The discovery of miRNAs as new and important regulators of gene expression is expected to broaden our biological understanding of the regulatory mechanism in muscle by adding another dimension of regulation to the diversity and complexity of gene-regulatory networks. As important regulators of muscle development, unravelling the regulatory circuits involved may be challenging, given that a single miRNA can regulate the expression of many mRNA targets. Although the identification of the regulatory targets of miRNAs in muscle is a challenge, it will be critical for placing them in genetic pathways and biological contexts. Therefore, combining informatics, biochemical and genetic approaches will not only expected to reveal the elucidation of the miRNA regulatory network in skeletal muscle and to bring a better knowledge on muscle tissue regulation but will also raise new opportunities for therapeutic intervention in muscular dystrophies by identifying candidate miRNAs as potential targets for clinical application.

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