Journal
NEUROBIOLOGY OF AGING
Volume 64, Issue -, Pages 123-138Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2017.12.020
Keywords
Amyotrophic lateral sclerosis; MicroRNAs; Biomarkers; miR-142-3p; miR-1249-3p
Categories
Funding
- Millennium Institute [P09-015-F]
- FONDAP program [15150012]
- Frick Foundation [20014-15]
- ALS Therapy Alliance [2014-F-059]
- Muscular Dystrophy Association [382453]
- CONICYT-USA [2013-0003]
- Michael J Fox Foundation for Parkinson's Research-Target Validation [9277]
- COPEC-UC Foundation [2013.R.40]
- Ecos-Conicyt [C13S02]
- FONDECYT [1140549, 1161284]
- Office of Naval Research-Global (ONR-G) [N62909-16-1-2003]
- ALSRP Therapeutic Idea Award [AL150111, 2014-F-034]
- CONICYT [22130888, 21151265]
- CONICYT Ring Initiative [ACT1109]
- CONICYT DRI USA [2013-0030]
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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. (C) 2017 Elsevier Inc. All rights reserved.
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