Genome-wide circulating microRNA expression profiling reveals potential biomarkers for amyotrophic lateral sclerosis.
Neurobiol Aging
; 64: 123-138, 2018 04.
Article
en En
| MEDLINE
| ID: mdl-29458840
The occurrence of mutations of TDP-43, FUS, and C9ORF72 in amyotrophic lateral sclerosis (ALS) suggests pathogenic alterations to RNA metabolism and specifically to microRNA (miRNA) biology. Moreover, several ALS-related proteins impact stress granule dynamics affecting miRNA biogenesis and cellular miRNA levels. miRNAs are present in different biological fluids and have been proposed as potential biomarkers. Here we used next-generation sequencing to perform a comparative analysis of the expression profile of circulating miRNAs in the serum of 2 mutant superoxide dismutase 1 transgenic mice. Top hit candidates were then validated using quantitative real-time polymerase chain reaction, confirming significant changes for 6 miRNAs. In addition, one of these miRNAs was also altered in mutant TDP-43 mice. Then, we tested this set of miRNAs in the serum from sporadic ALS patients, observing a significant deregulation of hsa-miR-142-3p and hsa-miR-1249-3p. A negative correlation between the revised ALS functional rating scale and hsa-miR-142-3p levels was found. Bioinformatics analysis of the regulatory network governed by hsa-miR-142-3p identified TDP-43 and C9orf72 as possible targets, suggesting a connection with ALS pathogenesis. This study identifies miRNAs that are altered in ALS that may serve as potentials biomarkers.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Estudio de Asociación del Genoma Completo
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Transcriptoma
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MicroARN Circulante
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Esclerosis Amiotrófica Lateral
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Aged
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Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Neurobiol Aging
Año:
2018
Tipo del documento:
Article