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MIRNA EXPRESSION IN CONTROL AND FSHD FETAL HUMAN MUSCLE BIOPSIES
Author
Affilliation
Sorbonne Universités, UPMC Univ Paris 06, Center of Research in Myology UM76, Paris, France / INSERM UMRS974. Paris, France / CNRS FRE 3617, F-75013. Paris, France / Institut de Myologie, F-75013. Paris, France / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisas sobre o o Timo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisas sobre o Timo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto de Pesquisa de Clínica Evandro Chagas. Laboratório de Pesquisa Clínica em DST-AIDS. Rio de Janeiro, RJ, Brasil.
CNRS FRE 3377, Université Paris-Sud CEA Saclay, Gif-sur-Yvette, France.
Aix Marseille Université. Faculté de Médecine de la Timone. Laboratoire de Génétique Médicale et Génomique Fonctionnelle, INSERM UMRS 910. Marseille, France.
Aix Marseille Université. Faculté de Médecine de la Timone. Laboratoire de Génétique Médicale et Génomique Fonctionnelle, INSERM UMRS 910. Marseille, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisas sobre o Timo. Rio de Janeiro, RJ, Brasil.
CNRS FRE 3377, Université Paris-Sud CEA Saclay, Gif-sur-Yvette, France.
CNRS FRE 3377, Université Paris-Sud CEA Saclay, Gif-sur-Yvette, France.
Sorbonne Universités, UPMC Univ Paris 06, Center of Research in Myology UM76, Paris, France / INSERM UMRS974. Paris, France / CNRS FRE 3617, F-75013. Paris, France / Institut de Myologie, F-75013. Paris, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisas sobre o Timo. Rio de Janeiro, RJ, Brasil.
Sorbonne Universités, UPMC Univ Paris 06, Center of Research in Myology UM76, Paris, France / INSERM UMRS974. Paris, France / CNRS FRE 3617, F-75013. Paris, France / Institut de Myologie, F-75013. Paris, France.
Sorbonne Universités, UPMC Univ Paris 06, Center of Research in Myology UM76, Paris, France / INSERM UMRS974. Paris, France / CNRS FRE 3617, F-75013. Paris, France / Institut de Myologie, F-75013. Paris, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisas sobre o Timo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto de Pesquisa de Clínica Evandro Chagas. Laboratório de Pesquisa Clínica em DST-AIDS. Rio de Janeiro, RJ, Brasil.
CNRS FRE 3377, Université Paris-Sud CEA Saclay, Gif-sur-Yvette, France.
Aix Marseille Université. Faculté de Médecine de la Timone. Laboratoire de Génétique Médicale et Génomique Fonctionnelle, INSERM UMRS 910. Marseille, France.
Aix Marseille Université. Faculté de Médecine de la Timone. Laboratoire de Génétique Médicale et Génomique Fonctionnelle, INSERM UMRS 910. Marseille, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisas sobre o Timo. Rio de Janeiro, RJ, Brasil.
CNRS FRE 3377, Université Paris-Sud CEA Saclay, Gif-sur-Yvette, France.
CNRS FRE 3377, Université Paris-Sud CEA Saclay, Gif-sur-Yvette, France.
Sorbonne Universités, UPMC Univ Paris 06, Center of Research in Myology UM76, Paris, France / INSERM UMRS974. Paris, France / CNRS FRE 3617, F-75013. Paris, France / Institut de Myologie, F-75013. Paris, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisas sobre o Timo. Rio de Janeiro, RJ, Brasil.
Sorbonne Universités, UPMC Univ Paris 06, Center of Research in Myology UM76, Paris, France / INSERM UMRS974. Paris, France / CNRS FRE 3617, F-75013. Paris, France / Institut de Myologie, F-75013. Paris, France.
Sorbonne Universités, UPMC Univ Paris 06, Center of Research in Myology UM76, Paris, France / INSERM UMRS974. Paris, France / CNRS FRE 3617, F-75013. Paris, France / Institut de Myologie, F-75013. Paris, France.
Abstract
BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disorder and is one of the most common forms of muscular dystrophy. We have recently shown that some hallmarks of FSHD are already expressed in fetal FSHD biopsies, thus opening a new field of investigation for mechanisms leading to FSHD. As microRNAs (miRNAs) play an important role in myogenesis and muscle disorders, in this study we compared miRNAs expression levels during normal and FSHD muscle development. METHODS: Muscle biopsies were obtained from quadriceps of both healthy control and FSHD1 fetuses with ages ranging from 14 to 33 weeks of development. miRNA expression profiles were analyzed using TaqMan Human MicroRNA Arrays. RESULTS: During human skeletal muscle development, in control muscle biopsies we observed changes for 4 miRNAs potentially involved in secondary muscle fiber formation and 5 miRNAs potentially involved in fiber maturation. When we compared the miRNA profiles obtained from control and FSHD biopsies, we did not observe any differences in the muscle specific miRNAs. However, we identified 8 miRNAs exclusively expressed in FSHD1 samples (miR-330, miR-331-5p, miR-34a, miR-380-3p, miR-516b, miR-582-5p, miR-517* and miR-625) which could represent new biomarkers for this disease. Their putative targets are mainly involved in muscle development and morphogenesis. Interestingly, these FSHD1 specific miRNAs do not target the genes previously described to be involved in FSHD. CONCLUSIONS:
This work provides new candidate mechanisms potentially involved in the onset of FSHD pathology. Whether these FSHD specific miRNAs cause deregulations during fetal development, or protect against the appearance of the FSHD phenotype until the second decade of life still needs to be investigated.
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