Dysregulated miRNAs and their pathogenic implications for the neurometabolic disease propionic acidemia

Abstract 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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ana Rivera-Barahona, Alejandro Fulgencio-Covián, Celia Pérez-Cerdá, Ricardo Ramos, Michael A. Barry, Magdalena Ugarte, Belén Pérez, Eva Richard, Lourdes R Desviat
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/81f02db56c494ec3a74cb8d4bc20b7c9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:81f02db56c494ec3a74cb8d4bc20b7c9
record_format	dspace
spelling	oai:doaj.org-article:81f02db56c494ec3a74cb8d4bc20b7c92021-12-02T12:32:57ZDysregulated miRNAs and their pathogenic implications for the neurometabolic disease propionic acidemia10.1038/s41598-017-06420-82045-2322https://doaj.org/article/81f02db56c494ec3a74cb8d4bc20b7c92017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06420-8https://doaj.org/toc/2045-2322Abstract 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.Ana Rivera-BarahonaAlejandro Fulgencio-CoviánCelia Pérez-CerdáRicardo RamosMichael A. BarryMagdalena UgarteBelén PérezEva RichardLourdes R DesviatNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ana Rivera-Barahona Alejandro Fulgencio-Covián Celia Pérez-Cerdá Ricardo Ramos Michael A. Barry Magdalena Ugarte Belén Pérez Eva Richard Lourdes R Desviat Dysregulated miRNAs and their pathogenic implications for the neurometabolic disease propionic acidemia
description	Abstract 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.
format	article
author	Ana Rivera-Barahona Alejandro Fulgencio-Covián Celia Pérez-Cerdá Ricardo Ramos Michael A. Barry Magdalena Ugarte Belén Pérez Eva Richard Lourdes R Desviat
author_facet	Ana Rivera-Barahona Alejandro Fulgencio-Covián Celia Pérez-Cerdá Ricardo Ramos Michael A. Barry Magdalena Ugarte Belén Pérez Eva Richard Lourdes R Desviat
author_sort	Ana Rivera-Barahona
title	Dysregulated miRNAs and their pathogenic implications for the neurometabolic disease propionic acidemia
title_short	Dysregulated miRNAs and their pathogenic implications for the neurometabolic disease propionic acidemia
title_full	Dysregulated miRNAs and their pathogenic implications for the neurometabolic disease propionic acidemia
title_fullStr	Dysregulated miRNAs and their pathogenic implications for the neurometabolic disease propionic acidemia
title_full_unstemmed	Dysregulated miRNAs and their pathogenic implications for the neurometabolic disease propionic acidemia
title_sort	dysregulated mirnas and their pathogenic implications for the neurometabolic disease propionic acidemia
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/81f02db56c494ec3a74cb8d4bc20b7c9
work_keys_str_mv	AT anariverabarahona dysregulatedmirnasandtheirpathogenicimplicationsfortheneurometabolicdiseasepropionicacidemia AT alejandrofulgenciocovian dysregulatedmirnasandtheirpathogenicimplicationsfortheneurometabolicdiseasepropionicacidemia AT celiaperezcerda dysregulatedmirnasandtheirpathogenicimplicationsfortheneurometabolicdiseasepropionicacidemia AT ricardoramos dysregulatedmirnasandtheirpathogenicimplicationsfortheneurometabolicdiseasepropionicacidemia AT michaelabarry dysregulatedmirnasandtheirpathogenicimplicationsfortheneurometabolicdiseasepropionicacidemia AT magdalenaugarte dysregulatedmirnasandtheirpathogenicimplicationsfortheneurometabolicdiseasepropionicacidemia AT belenperez dysregulatedmirnasandtheirpathogenicimplicationsfortheneurometabolicdiseasepropionicacidemia AT evarichard dysregulatedmirnasandtheirpathogenicimplicationsfortheneurometabolicdiseasepropionicacidemia AT lourdesrdesviat dysregulatedmirnasandtheirpathogenicimplicationsfortheneurometabolicdiseasepropionicacidemia
_version_	1718393929104097280

Dysregulated miRNAs and their pathogenic implications for the neurometabolic disease propionic acidemia

Ejemplares similares