MicroRNAs in hereditary and sporadic premature aging syndromes and other laminopathies
Résumé
Hereditary and sporadic laminopathies are caused by mutations in genes encoding lamins, their partners, or the metalloprotease ZMPSTE24/FACE1. Depending on the clinical phenotype, they are classified as tissue-specific or systemic diseases. The latter mostly manifest with several accelerated aging features, as in Hutchinson-Gil-ford progeria syndrome (HGPS) and other progeroid syndromes. MicroRNAs are small noncoding RNAs described as powerful regulators of gene expression, mainly by degrading target mRNAs or by inhibiting their translation. In recent years, the role of these small RNAs has become an object of study in laminopathies using in vitro or in vivo murine models as well as cells/tissues of patients. To date, few miRNAs have been reported to exert protective effects in laminopathies, including miR-9, which prevents progerin accumulation in HGPS neurons. The recent literature has described the potential implication of several other miRNAs in the patho-physiology of laminopathies, mostly by exerting deleterious effects. This review provides an overview of the current knowledge of the functional relevance and molecular insights of miRNAs in laminopathies. Furthermore, we discuss how these discoveries could help to better understand these diseases at the molecular level and could pave the way toward identifying new potential therapeutic targets and strategies based on miRNA modulation.
Mots clés
mRNAs
HGPS
HGPS-like
Hutchinson-Gilford progeria-like syndromes
hMSCs
human mesenchymal stem cells
hsa
Homo sapiens
IGF-1
insulin-like growth factor-1
INM
inner nuclear membrane
iPSCs
induced pluripotent stem cells
and leukomelanodermic papules
lncRNA
MAD
long-noncoding RNA
Mouse embryonic fibroblasts
Mandibuloacral dysplasia
miRNAs
MEFs
LGMD1B
limb-girdle muscular dystrophy type 1B
Nuclear pore complex
Nucleotides
ORF
open reading frame
RD
Restrictive dermopathy
Reactive oxygen species
ROS
VSMCs
Vascular smooth muscle cells dedifferentiation
ASCs
Acquired partial lipodystrophy
APLD
MicroRNA expression
Lamins
Laminopathies
Argonaute protein
AGO
adult-onset autosomal-dominant leukodystrophy
ADLD
Aging
Genetics
Hutchinson-Gilford progeria syndrome
nuclear envelope transmembrane partner proteins
NLS
NPC
Nuclear localization signal
ceRNA
Werner syndrome
AWS
Adipose stem cells
CMT2B1
congenital muscular dystrophy
competing endogenous RNA
CMD
DCM1A
Charcot-Marie-Tooth disease type 2B1
EDMD
Dilated cardiomyopathy type 1A
FPLD2
Dunnigan-type familial partial lipodystrophy
Emery-Dreifuss muscular dystrophy
Mmu
hepatitis C virus
HCV
Mus musculus
microRNAs
lamin-associated domains
LAD
hypertrophic cardiomyopathy
hepatic steatosis
LIRLLC
lipoatrophy with diabetes
NETs
Mesenchymal stem cells
Messenger RNAs
MSCs
Origine : Publication financée par une institution
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