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Noncoding RNAs in Duchenne and Becker muscular dystrophies: role in pathogenesis and future prognostic and therapeutic perspectives

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Abstract

Noncoding RNAs (ncRNAs), such as miRNAs and long noncoding RNAs, are key regulators of gene expression at the post-transcriptional level and represent promising therapeutic targets and biomarkers for several human diseases, including Duchenne and Becker muscular dystrophies (DMD/BMD). A role for ncRNAs in the pathogenesis of muscular dystrophies has been suggested, even if it is still incompletely understood. Here, we discuss current progress leading towards the clinical utility of ncRNAs for DMD/BMD. Long and short noncoding RNAs are differentially expressed in DMD/BMD and have a mechanism of action via targeting mRNAs. A subset of muscle-enriched miRNAs, the so-called myomiRs (miR-1, miR-133, and miR-206), are increased in the serum of patients with DMD and in dystrophin-defective animal models. Interestingly, myomiRs might be used as biomarkers, given that their levels can be corrected after dystrophin restoration in dystrophic mice. Remarkably, further evidence demonstrates that ncRNAs also play a role in dystrophin expression; thus, their modulations might represent a potential therapeutic strategy with the aim of upregulating the dystrophin protein in combination with other oligonucleotides/gene therapy approaches.

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Acknowledgements

We gratefully thank the Associazione Centro Dino Ferrari for its support.

Funding

The project received partial support from Italian Ministry of Health to GPC.

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Authors and Affiliations

  1. Neurology Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Roberta Brusa, Francesca Magri, Nereo Bresolin & Stefania Corti

  2. Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Milan, Italy

    Nereo Bresolin, Giacomo Pietro Comi & Stefania Corti

  3. Neuromuscular and Rare Diseases Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Giacomo Pietro Comi

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  1. Roberta Brusa
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  2. Francesca Magri
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RB, FM and SC conceived and wrote the manuscript, NB and GPC revised the text.

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Correspondence to Stefania Corti.

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Brusa, R., Magri, F., Bresolin, N. et al. Noncoding RNAs in Duchenne and Becker muscular dystrophies: role in pathogenesis and future prognostic and therapeutic perspectives. Cell. Mol. Life Sci. 77, 4299–4313 (2020). https://doi.org/10.1007/s00018-020-03537-4

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