The lncRNA 44s2 Study Applicability to the Design of 45-55 Exon Skipping Therapeutic Strategy for DMD.

Autor: Gargaun E; SU, INSERM UMRS974, AIM, Center of Research in Myology, Pitié-Salpêtrière Hospital, 75013 Paris, France., Falcone S; SU, INSERM UMRS974, AIM, Center of Research in Myology, Pitié-Salpêtrière Hospital, 75013 Paris, France., Solé G; Centre de Référence des Maladies Neuromusculaires AOC, Service de Neuropédiatrie, CHU Bordeaux, 33000 Bordeaux, France., Durigneux J; Centre de Référence des Maladies Neuromusculaires AOC, CHU Angers, 49933 Angers, France., Urtizberea A; Institute of Myology, Hôpital Pitié-Salpêtrière, 75013 Paris, France., Cuisset JM; Centre de Référence des Maladies Neuromusculaires Nord/Est/Ile de France, Service de Médecine Physique et de Réadaptation, CHRU de Lille, 59000 Lille, France., Benkhelifa-Ziyyat S; SU, INSERM UMRS974, AIM, Center of Research in Myology, Pitié-Salpêtrière Hospital, 75013 Paris, France., Julien L; SU, INSERM UMRS974, AIM, Center of Research in Myology, Pitié-Salpêtrière Hospital, 75013 Paris, France., Boland A; CEA, Centre National de Recherche en Génomique Humaine, Université Paris-Saclay, 91057 Evry, France., Sandron F; CEA, Centre National de Recherche en Génomique Humaine, Université Paris-Saclay, 91057 Evry, France., Meyer V; CEA, Centre National de Recherche en Génomique Humaine, Université Paris-Saclay, 91057 Evry, France., Deleuze JF; CEA, Centre National de Recherche en Génomique Humaine, Université Paris-Saclay, 91057 Evry, France., Salgado D; INSERM, Marseille Medical Genetics, Aix Marseille University, 13005 Marseille, France., Desvignes JP; INSERM, Marseille Medical Genetics, Aix Marseille University, 13005 Marseille, France., Béroud C; INSERM, Marseille Medical Genetics, Aix Marseille University, 13005 Marseille, France.; Département de Génétique Médicale, APHM, Hôpital d'Enfants de la Timone, 13005 Marseille, France., Chessel A; Laboratoire d'Optiques et Biosciences (LOB), CNRS, INSERM, École polytechnique, Institut Polytechnique de Paris, 91120 Palaiseau, France., Blesius A; IRIS, Institut de Recherches Internationales Servier, 92150 Suresnes, France., Krahn M; INSERM, Marseille Medical Genetics, Aix Marseille University, 13005 Marseille, France.; Département de Génétique Médicale, APHM, Hôpital d'Enfants de la Timone, 13005 Marseille, France., Levy N; INSERM, Marseille Medical Genetics, Aix Marseille University, 13005 Marseille, France.; Département de Génétique Médicale, APHM, Hôpital d'Enfants de la Timone, 13005 Marseille, France., Leturcq F; AP-HP, Laboratoire de génétique et biologie moléculaires, Hôpital Cochin, Université Paris Descartes-Sorbonne Paris Cité, 75014 Paris, France., Pietri-Rouxel F; SU, INSERM UMRS974, AIM, Center of Research in Myology, Pitié-Salpêtrière Hospital, 75013 Paris, France.
Jazyk: angličtina
Zdroj: Biomedicines [Biomedicines] 2021 Feb 20; Vol. 9 (2). Date of Electronic Publication: 2021 Feb 20.
DOI: 10.3390/biomedicines9020219
Abstrakt: In skeletal muscle, long noncoding RNAs (lncRNAs) are involved in dystrophin protein stabilization but also in the regulation of myocytes proliferation and differentiation. Hence, they could represent promising therapeutic targets and/or biomarkers for Duchenne and Becker muscular dystrophy (DMD/BMD). DMD and BMD are X-linked myopathies characterized by a progressive muscular dystrophy with or without dilatative cardiomyopathy. Two-thirds of DMD gene mutations are represented by deletions, and 63% of patients carrying DMD deletions are eligible for 45 to 55 multi-exons skipping (MES), becoming BMD patients (BMDΔ45-55). We analyzed the genomic lncRNA presence in 38 BMDΔ45-55 patients and characterized the lncRNA localized in introns 44 and 55 of the DMD gene. We highlighted that all four lncRNA are differentially expressed during myogenesis in immortalized and primary human myoblasts. In addition, the lncRNA44s2 was pointed out as a possible accelerator of differentiation. Interestingly, lncRNA44s expression was associated with a favorable clinical phenotype. These findings suggest that lncRNA44s2 could be involved in muscle differentiation process and become a potential disease progression biomarker. Based on these results, we support MES45-55 therapy and propose that the design of the CRISPR/Cas9 MES45-55 assay consider the lncRNA sequences bordering the exonic 45 to 55 deletion.
Databáze: MEDLINE
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