Genome-wide circulating microRNA expression profiling reveals potential biomarkers for amyotrophic lateral sclerosis
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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.
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
Artículo de publicación ISI
Quote ItemNeurobiology of Aging, 64 (2018): 123-138
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