Identification of a circulating miRNA signature in extracellular vesicles collected from amyotrophic lateral sclerosis patients.
Brain Res
; 1708: 100-108, 2019 04 01.
Article
em En
| MEDLINE
| ID: mdl-30552897
ABSTRACT
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder associated with the progressive death of motor neurons. Mean survival for a patient diagnosed with ALS is between 2 and 5â¯years. Early and efficient diagnosis of the various forms of ALS remains a significant challenge, resulting in a need to identify clinically-relevant biomarkers in readily accessible body fluids. microRNAs (miRNAs) are short, evolutionarily conserved non-coding RNA molecules involved in post-transcriptional regulation of gene expression that have received interest as disease biomarkers. This study was undertaken to identify an ALS-associated miRNA signature in extracellular vesicles (EVs), which can cross the blood-brain barrier and enter the circulatory system, obtained from plasma samples of persons diagnosed and living with ALS (PALS). Next-generation sequencing was used to identify differentially expressed miRNAs recovered from EVs of PALS and healthy controls. High-throughput sequencing data for select miRNA targets was subsequently validated by droplet digital PCR (ddPCR). This approach revealed elevated levels of 5 miRNAs and reduced levels of 22 miRNAs in EVs collected from PALS as compared with healthy controls subjects. miRNAs with relevance to ALS were found to be deregulated, including miR-9-5p, miR-183-5p, miR-338-3p and miR-1246. MiR-15a-5p and miR-193a-5p were identified for their diagnostic potential of ALS and association with disability progression, respectively. Functional assessment of transcripts targeted by select ALS-associated miRNAs revealed processes such as transcriptional regulation and protein ubiquitination. These data identify an ALS-associated miRNAs signature in EVs of PALS and further strengthen the potential diagnostic relevance of these small molecules for this condition.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
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Vesículas Extracelulares
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Esclerose Lateral Amiotrófica
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Brain Res
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Canadá