PMID- 36265896
OWN - NLM
STAT- MEDLINE
DCOM- 20221025
LR  - 20230213
IS  - 2575-1077 (Electronic)
IS  - 2575-1077 (Linking)
VI  - 6
IP  - 1
DP  - 2023 Jan
TI  - Dlk1-Dio3 cluster miRNAs regulate mitochondrial functions in the dystrophic 
      muscle in Duchenne muscular dystrophy.
LID - 10.26508/lsa.202201506 [doi]
LID - e202201506
AB  - Duchenne muscular dystrophy (DMD) is a severe muscle disease caused by impaired 
      expression of dystrophin. Whereas mitochondrial dysfunction is thought to play an 
      important role in DMD, the mechanism of this dysfunction remains to be clarified. 
      Here we demonstrate that in DMD and other muscular dystrophies, a large number of 
      Dlk1-Dio3 clustered miRNAs (DD-miRNAs) are coordinately up-regulated in 
      regenerating myofibers and in the serum. To characterize the biological effect of 
      this dysregulation, 14 DD-miRNAs were simultaneously overexpressed in vivo in 
      mouse muscle. Transcriptomic analysis revealed highly similar changes between the 
      muscle ectopically overexpressing 14 DD-miRNAs and the mdx diaphragm, with 
      naturally up-regulated DD-miRNAs. Among the commonly dysregulated pathway we 
      found repressed mitochondrial metabolism, and oxidative phosphorylation (OxPhos) 
      in particular. Knocking down the DD-miRNAs in iPS-derived skeletal myotubes 
      resulted in increased OxPhos activities. The data suggest that (1) DD-miRNAs are 
      important mediators of dystrophic changes in DMD muscle, (2) mitochondrial 
      metabolism and OxPhos in particular are targeted in DMD by coordinately 
      up-regulated DD-miRNAs. These findings provide insight into the mechanism of 
      mitochondrial dysfunction in muscular dystrophy.
CI  - (c) 2022 Vu Hong et al.
FAU - Vu Hong, Ai
AU  - Vu Hong A
AD  - Genethon, Evry, France.
AD  - Universite Paris-Saclay, Univ Evry, Inserm, Genethon, Integrare Research Unit 
      UMR_S951, Evry, France.
FAU - Bourg, Nathalie
AU  - Bourg N
AD  - Genethon, Evry, France.
AD  - Universite Paris-Saclay, Univ Evry, Inserm, Genethon, Integrare Research Unit 
      UMR_S951, Evry, France.
FAU - Sanatine, Peggy
AU  - Sanatine P
AD  - Genethon, Evry, France.
AD  - Universite Paris-Saclay, Univ Evry, Inserm, Genethon, Integrare Research Unit 
      UMR_S951, Evry, France.
FAU - Poupiot, Jerome
AU  - Poupiot J
AD  - Genethon, Evry, France.
AD  - Universite Paris-Saclay, Univ Evry, Inserm, Genethon, Integrare Research Unit 
      UMR_S951, Evry, France.
FAU - Charton, Karine
AU  - Charton K
AUID- ORCID: 0000-0001-7419-140X
AD  - Genethon, Evry, France.
AD  - Universite Paris-Saclay, Univ Evry, Inserm, Genethon, Integrare Research Unit 
      UMR_S951, Evry, France.
FAU - Gicquel, Evelyne
AU  - Gicquel E
AD  - Genethon, Evry, France.
AD  - Universite Paris-Saclay, Univ Evry, Inserm, Genethon, Integrare Research Unit 
      UMR_S951, Evry, France.
FAU - Massourides, Emmanuelle
AU  - Massourides E
AUID- ORCID: 0000-0002-9829-5008
AD  - CECS, I-STEM, UEVE INSERM UMR861, AFM, Corbeil-Essonnes, France.
FAU - Spinazzi, Marco
AU  - Spinazzi M
AD  - Neuromuscular Reference Center, Department of Neurology, CHU d'Angers, Angers, 
      France.
AD  - Institute of Neurobiology and Neuropathology CHU d'Angers, Angers, France.
FAU - Richard, Isabelle
AU  - Richard I
AD  - Genethon, Evry, France.
AD  - Universite Paris-Saclay, Univ Evry, Inserm, Genethon, Integrare Research Unit 
      UMR_S951, Evry, France.
FAU - Israeli, David
AU  - Israeli D
AUID- ORCID: 0000-0003-2762-2195
AD  - Genethon, Evry, France israeli@genethon.fr.
AD  - Universite Paris-Saclay, Univ Evry, Inserm, Genethon, Integrare Research Unit 
      UMR_S951, Evry, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221020
PL  - United States
TA  - Life Sci Alliance
JT  - Life science alliance
JID - 101728869
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Dlk1 protein, mouse)
RN  - 0 (Dystrophin)
RN  - 0 (MicroRNAs)
RN  - EC 1.11.1.- (iodothyronine deiodinase type III)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Calcium-Binding Proteins/metabolism
MH  - Dystrophin
MH  - Mice, Inbred mdx
MH  - *MicroRNAs/genetics/metabolism
MH  - Mitochondria/genetics/metabolism
MH  - Muscle, Skeletal/metabolism
MH  - *Muscular Dystrophy, Duchenne/metabolism
PMC - PMC9585966
COIS- The authors declare that they have no conflict of interest.
EDAT- 2022/10/21 06:00
MHDA- 2022/10/25 06:00
PMCR- 2022/10/20
CRDT- 2022/10/20 20:42
PHST- 2022/04/28 00:00 [received]
PHST- 2022/10/04 00:00 [revised]
PHST- 2022/10/04 00:00 [accepted]
PHST- 2022/10/20 20:42 [entrez]
PHST- 2022/10/21 06:00 [pubmed]
PHST- 2022/10/25 06:00 [medline]
PHST- 2022/10/20 00:00 [pmc-release]
AID - 6/1/e202201506 [pii]
AID - LSA-2022-01506 [pii]
AID - 10.26508/lsa.202201506 [doi]
PST - epublish
SO  - Life Sci Alliance. 2022 Oct 20;6(1):e202201506. doi: 10.26508/lsa.202201506. 
      Print 2023 Jan.