miR-379 links glucocorticoid treatment with mitochondrial response in Duchenne muscular dystrophy.

Mitochondrial Proton-Translocating ATPases/antagonists & inhibitors/genetics/metabolism; Muscle, Skeletal/metabolism; Muscular Dystrophy, Duchenne/drug therapy/genetics; Myoblasts, Skeletal/metabolism; RNA Interference; RNA, Small Interfering/metabolism

Abstract :

[en] Duchenne Muscular Dystrophy (DMD) is a lethal muscle disorder, caused by mutations in the DMD gene and affects approximately 1:5000-6000 male births. In this report, we identified dysregulation of members of the Dlk1-Dio3 miRNA cluster in muscle biopsies of the GRMD dog model. Of these, we selected miR-379 for a detailed investigation because its expression is high in the muscle, and is known to be responsive to glucocorticoid, a class of anti-inflammatory drugs commonly used in DMD patients. Bioinformatics analysis predicts that miR-379 targets EIF4G2, a translational factor, which is involved in the control of mitochondrial metabolic maturation. We confirmed in myoblasts that EIF4G2 is a direct target of miR-379, and identified the DAPIT mitochondrial protein as a translational target of EIF4G2. Knocking down DAPIT in skeletal myotubes resulted in reduced ATP synthesis and myogenic differentiation. We also demonstrated that this pathway is GC-responsive since treating mice with dexamethasone resulted in reduced muscle expression of miR-379 and increased expression of EIF4G2 and DAPIT. Furthermore, miR-379 seric level, which is also elevated in the plasma of DMD patients in comparison with age-matched controls, is reduced by GC treatment. Thus, this newly identified pathway may link GC treatment to a mitochondrial response in DMD.

Disciplines :

Pediatrics
Neurology

Author, co-author :

Sanson, M.

Vu Hong, A.

Massourides, E.

Bourg, N.

Suel, L.

Amor, F.

Corre, G.

Bénit, P.

Barthélémy, I.

Blot, S.

More authors (7 more)

Language :

English

Title :

miR-379 links glucocorticoid treatment with mitochondrial response in Duchenne muscular dystrophy.

Publication date :

04 June 2020

Journal title :

Scientific Reports

eISSN :

2045-2322

Publisher :

Nature Publishing Group, London, United Kingdom

Volume :

Issue :

Pages :

9139

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

doi: 10.1038/s41598-020-66016-7

Available on ORBi :

since 01 February 2021

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