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Dysregulated miRNAs and their pathogenic implications for the neurometabolic
disease propionic acidemia
#MMPMID28720782
Rivera-Barahona A
; Fulgencio-Covián A
; Pérez-Cerdá C
; Ramos R
; Barry MA
; Ugarte M
; Pérez B
; Richard E
; Desviat LR
Sci Rep
2017[Jul]; 7
(1
): 5727
PMID28720782
show ga
miRNome expression profiling was performed in a mouse model of propionic acidemia
(PA) and in patients' plasma samples to investigate the role of miRNAs in the
pathophysiology of the disease and to identify novel biomarkers and therapeutic
targets. PA is a potentially lethal neurometabolic disease with patients
developing neurological deficits and cardiomyopathy in the long-term, among other
complications. In the PA mouse liver we identified 14 significantly dysregulated
miRNAs. Three selected miRNAs, miR-34a-5p, miR-338-3p and miR-350, were found
upregulated in brain and heart tissues. Predicted targets involved in apoptosis,
stress-signaling and mitochondrial function, were inversely found down-regulated.
Functional analysis with miRNA mimics in cellular models confirmed these
findings. miRNA profiling in plasma samples from neonatal PA patients and
age-matched control individuals identified a set of differentially expressed
miRNAs, several were coincident with those identified in the PA mouse, among them
miR-34a-5p and miR-338-3p. These two miRNAs were also found dysregulated in
childhood and adult PA patients' cohorts. Taken together, the results reveal
miRNA signatures in PA useful to identify potential biomarkers, to refine the
understanding of the molecular mechanisms of this rare disease and, eventually,
to improve the management of patients.
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