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Defective Regulation of MicroRNA Target Genes in Myoblasts from Facioscapulohumeral Dystrophy Patients
- Source :
- Journal of Biological Chemistry, Journal of Biological Chemistry, 2013, 288 (49), pp.34989-35002. ⟨10.1074/jbc.M113.504522⟩, Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2013, 288 (49), pp.34989-35002. ⟨10.1074/jbc.M113.504522⟩
- Publication Year :
- 2013
- Publisher :
- HAL CCSD, 2013.
-
Abstract
- Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant hereditary neuromuscular disorder linked to the deletion of an integral number of 3.3-kb-long macrosatellite repeats (D4Z4) within the subtelomeric region of chromosome 4q. Most genes identified in this region are overexpressed in FSHD myoblasts, including the double homeobox genes DUX4 and DUX4c. We have carried out a simultaneous miRNome/transcriptome analysis of FSHD and control primary myoblasts. Of 365 microRNAs (miRNAs) analyzed in this study, 29 were found to be differentially expressed between FSHD and normal myoblasts. Twenty-one microRNAs (miR-1, miR-7, miR-15a, miR-22, miR-30e, miR-32, miR-107, miR-133a, miR-133b, miR-139, miR-152, miR-206, miR-223, miR-302b, miR-331, miR-362, miR-365, miR-382, miR-496, miR-532, miR-654, and miR-660) were up-regulated, and eight were down-regulated (miR-15b, miR-20b, miR-21, miR-25, miR-100, miR-155, miR-345, and miR-594). Twelve of the miRNAs up-regulated in FHSD were also up-regulated in the cells ectopically expressing DUX4c, suggesting that this gene could regulate miRNA gene transcription. The myogenic miRNAs miR-1, miR-133a, miR-133b, and miR-206 were highly expressed in FSHD myoblasts, which nonetheless did not prematurely enter myogenic differentiation. This could be accounted for by the fact that in FSHD myoblasts, functionally important target genes, including cell cycle, DNA damage, and ubiquitination-related genes, escape myogenic microRNA-induced repression.
- Subjects :
- Male
[SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
Cellular differentiation
Muscle Development
Biochemistry
Transcriptome
0302 clinical medicine
Facioscapulohumeral muscular dystrophy
Muscular Dystrophy
Muscular dystrophy
Cells, Cultured
ComputingMilieux_MISCELLANEOUS
Genetics
0303 health sciences
Facioscapulohumeral Dystrophy
Molecular Bases of Disease
Cell Differentiation
MicroRNA
Middle Aged
Muscular Dystrophy, Facioscapulohumeral
Up-Regulation
Genetic Diseases
embryonic structures
[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
Female
Transcription
musculoskeletal diseases
Adult
congenital, hereditary, and neonatal diseases and abnormalities
Myoblasts, Skeletal
Down-Regulation
Biology
03 medical and health sciences
Young Adult
DUX4
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
medicine
[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
Humans
Transcription Regulation
Molecular Biology
Gene
030304 developmental biology
Homeodomain Proteins
Gene Expression Profiling
Cell Biology
medicine.disease
nervous system diseases
Gene expression profiling
MicroRNAs
Homeobox
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 00219258 and 1083351X
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry, Journal of Biological Chemistry, 2013, 288 (49), pp.34989-35002. ⟨10.1074/jbc.M113.504522⟩, Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2013, 288 (49), pp.34989-35002. ⟨10.1074/jbc.M113.504522⟩
- Accession number :
- edsair.doi.dedup.....a8a6ca42e7ec87b911e3ac260a5eae65