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Overexpression of microRNA-206 in the skeletal muscle from myotonic dystrophy type 1 patients

BACKGROUND: MicroRNAs are highly conserved, noncoding RNAs involved in post-transcriptional gene silencing. They have been shown to participate in a wide range of biological processes, including myogenesis and muscle regeneration. The goal of this study is to test the hypothesis that myo-miRs (myo =...

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Autores principales: Gambardella, Stefano, Rinaldi, Fabrizio, Lepore, Saverio M, Viola, Antonella, Loro, Emanuele, Angelini, Corrado, Vergani, Lodovica, Novelli, Giuseppe, Botta, Annalisa
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2880982/
https://www.ncbi.nlm.nih.gov/pubmed/20487562
http://dx.doi.org/10.1186/1479-5876-8-48
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author Gambardella, Stefano
Rinaldi, Fabrizio
Lepore, Saverio M
Viola, Antonella
Loro, Emanuele
Angelini, Corrado
Vergani, Lodovica
Novelli, Giuseppe
Botta, Annalisa
author_facet Gambardella, Stefano
Rinaldi, Fabrizio
Lepore, Saverio M
Viola, Antonella
Loro, Emanuele
Angelini, Corrado
Vergani, Lodovica
Novelli, Giuseppe
Botta, Annalisa
author_sort Gambardella, Stefano
collection PubMed
description BACKGROUND: MicroRNAs are highly conserved, noncoding RNAs involved in post-transcriptional gene silencing. They have been shown to participate in a wide range of biological processes, including myogenesis and muscle regeneration. The goal of this study is to test the hypothesis that myo-miRs (myo = muscle + miR = miRNA) expression is altered in muscle from patients affected by myotonic dystrophy type 1 (DM1), the most frequently inherited neuromuscular disease in adults. In order to gain better insights about the role of miRNAs in the DM1 pathogenesis, we have also analyzed the muscular expression of miR-103 and miR-107, which have been identified in silico as attractive candidates for binding to the DMPK mRNA. METHODS: To this aim, we have profiled the expression of miR-133 (miR-133a, miR-133b), miR-1, miR-181 (miR-181a, miR-181b, miR-181c) and miR-206, that are specifically induced during myogenesis in cardiac and skeletal muscle tissues. miR-103 and miR-107, highly expressed in brain, heart and muscle have also been included in this study. QRT-PCR experiments have been performed on RNA from vastus lateralis biopsies of DM1 patients (n = 7) and control subjects (n = 4). Results of miRNAs expression have been confirmed by Northern blot, whereas in situ hybridization technique have been performed to localize misexpressed miRNAs on muscle sections from DM1 and control individuals. RESULTS: Only miR-206 showed an over-expression in 5 of 7 DM1 patients (threshold = 2, fold change between 1.20 and 13.22, average = 5.37) compared to the control group. This result has been further confirmed by Northern blot analysis (3.37-fold overexpression, R(2 )= 0.89). In situ hybridization localized miR-206 to nuclear site both in normal and DM1 tissues. Cellular distribution in DM1 tissues includes also the nuclear regions of centralized nuclei, with a strong signal corresponding to nuclear clumps. CONCLUSIONS: This work provides, for the first time, evidences about miRNAs misexpression in DM1 muscle tissues, adding a new element in the pathogenesis of this complex genetic disease.
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spelling pubmed-28809822010-06-05 Overexpression of microRNA-206 in the skeletal muscle from myotonic dystrophy type 1 patients Gambardella, Stefano Rinaldi, Fabrizio Lepore, Saverio M Viola, Antonella Loro, Emanuele Angelini, Corrado Vergani, Lodovica Novelli, Giuseppe Botta, Annalisa J Transl Med Research BACKGROUND: MicroRNAs are highly conserved, noncoding RNAs involved in post-transcriptional gene silencing. They have been shown to participate in a wide range of biological processes, including myogenesis and muscle regeneration. The goal of this study is to test the hypothesis that myo-miRs (myo = muscle + miR = miRNA) expression is altered in muscle from patients affected by myotonic dystrophy type 1 (DM1), the most frequently inherited neuromuscular disease in adults. In order to gain better insights about the role of miRNAs in the DM1 pathogenesis, we have also analyzed the muscular expression of miR-103 and miR-107, which have been identified in silico as attractive candidates for binding to the DMPK mRNA. METHODS: To this aim, we have profiled the expression of miR-133 (miR-133a, miR-133b), miR-1, miR-181 (miR-181a, miR-181b, miR-181c) and miR-206, that are specifically induced during myogenesis in cardiac and skeletal muscle tissues. miR-103 and miR-107, highly expressed in brain, heart and muscle have also been included in this study. QRT-PCR experiments have been performed on RNA from vastus lateralis biopsies of DM1 patients (n = 7) and control subjects (n = 4). Results of miRNAs expression have been confirmed by Northern blot, whereas in situ hybridization technique have been performed to localize misexpressed miRNAs on muscle sections from DM1 and control individuals. RESULTS: Only miR-206 showed an over-expression in 5 of 7 DM1 patients (threshold = 2, fold change between 1.20 and 13.22, average = 5.37) compared to the control group. This result has been further confirmed by Northern blot analysis (3.37-fold overexpression, R(2 )= 0.89). In situ hybridization localized miR-206 to nuclear site both in normal and DM1 tissues. Cellular distribution in DM1 tissues includes also the nuclear regions of centralized nuclei, with a strong signal corresponding to nuclear clumps. CONCLUSIONS: This work provides, for the first time, evidences about miRNAs misexpression in DM1 muscle tissues, adding a new element in the pathogenesis of this complex genetic disease. BioMed Central 2010-05-20 /pmc/articles/PMC2880982/ /pubmed/20487562 http://dx.doi.org/10.1186/1479-5876-8-48 Text en Copyright ©2010 Gambardella et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Gambardella, Stefano
Rinaldi, Fabrizio
Lepore, Saverio M
Viola, Antonella
Loro, Emanuele
Angelini, Corrado
Vergani, Lodovica
Novelli, Giuseppe
Botta, Annalisa
Overexpression of microRNA-206 in the skeletal muscle from myotonic dystrophy type 1 patients
title Overexpression of microRNA-206 in the skeletal muscle from myotonic dystrophy type 1 patients
title_full Overexpression of microRNA-206 in the skeletal muscle from myotonic dystrophy type 1 patients
title_fullStr Overexpression of microRNA-206 in the skeletal muscle from myotonic dystrophy type 1 patients
title_full_unstemmed Overexpression of microRNA-206 in the skeletal muscle from myotonic dystrophy type 1 patients
title_short Overexpression of microRNA-206 in the skeletal muscle from myotonic dystrophy type 1 patients
title_sort overexpression of microrna-206 in the skeletal muscle from myotonic dystrophy type 1 patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2880982/
https://www.ncbi.nlm.nih.gov/pubmed/20487562
http://dx.doi.org/10.1186/1479-5876-8-48
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