Longitudinal Study of Three microRNAs in Duchenne Muscular Dystrophy and Becker Muscular Dystrophy
Por:
Trifunov S, Natera-de Benito D, Exposito Escudero JM, Ortez-Gonzalez CI, Medina J, Cuadras-Palleja D, Badosa C, Carrera L, Nascimento-Osorio A and Jimenez-Mallebrera C
Publicada:
21 abr 2020
Ahead of Print:
21 abr 2020
Resumen:
Our objective was to investigate the potential of three microRNAs, miR-181a-5p, miR-30c-5p, and miR-206 as prognostic biomarkers for long-term follow up of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) patients. We analyzed the expression of three microRNAs in serum of 18 patients (DMD 13, BMD 5) and 13 controls using droplet digital PCR. Over 4 years a minimum of two and a maximum of three measurements were performed at different time points in the same patient. Correlations between microRNA serum levels, age, and functional outcome measures were analyzed. We show the individual evolution of the levels of the three microRNAs in 12 patients and also the effect of corticosteroid treatment on microRNAs expression. We measure the expression of three microRNAs in the muscle of six DMD patients and also the expression of target genes for miR-30c. We found that levels of miR-30c and miR-206 remained significantly elevated in DMD patients relative to controls over the entire study length. The introduction of the corticosteroid treatment did not significantly influence the levels of these microRNAs. We report a trend for microRNA levels to decrease with age. Moreover, miR-206 expression levels are capable to distinguish DMD from BMD patients according to ROC analysis. We found miR-30c expression decreased in the muscle of DMD patients and marked upregulation of the target genes for this microRNA. MiR-30c and miR-206 represent sensitive biomarkers for DMD, while miR-206 may have an additional value to distinguish the DMD and BMD phenotype. This may be particularly relevant to assess the effectiveness of treatments aimed at converting the DMD to the less-severe BMD like phenotype.
Filiaciones:
Trifunov S:
Neuromuscular Unit, Neuropaediatrics Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Natera-de Benito D:
Neuromuscular Unit, Neuropaediatrics Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Exposito Escudero JM:
Neuromuscular Unit, Neuropaediatrics Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Ortez-Gonzalez CI:
Neuromuscular Unit, Neuropaediatrics Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Medina J:
Rehabilitation and Physical Unit Department, Hospital Sant Joan de Deu, Barcelona, Spain
Cuadras-Palleja D:
Statistics Unit, Fundación Sant Joan de Déu, Barcelona, Spain
Badosa C:
Neuromuscular Unit, Neuropaediatrics Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Carrera L:
Neuromuscular Unit, Neuropaediatrics Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Nascimento-Osorio A:
Neuromuscular Unit, Neuropaediatrics Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Jimenez-Mallebrera C:
Neuromuscular Unit, Neuropaediatrics Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
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