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Neurobiol Aging. 2018 Apr;64:123-138. doi: 10.1016/j.neurobiolaging.2017.12.020. Epub 2017 Dec 29.

Genome-wide circulating microRNA expression profiling reveals potential biomarkers for amyotrophic lateral sclerosis.

Author information

1
Biomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile; Department of Neurological Sciences, Faculty of Medicine, University of Chile, Santiago, Chile; Center for Genomics and Bioinformatics, Faculty of Sciences, Universidad Mayor, Santiago, Chile.
2
Center for Genomics and Bioinformatics, Faculty of Sciences, Universidad Mayor, Santiago, Chile.
3
Biomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile.
4
Biomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile; Neurounion Biomedical Foundation, Santiago, Chile.
5
Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, Santiago, Chile.
6
Department of Neurological Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
7
Center for Genomics and Bioinformatics, Faculty of Sciences, Universidad Mayor, Santiago, Chile. Electronic address: patricio.manque@umayor.cl.
8
Biomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile; Buck Institute for Research on Aging, Novato, CA, USA; Harvard School of Public Health, Boston, MA, USA. Electronic address: chetz@med.uchile.cl.

Abstract

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.

KEYWORDS:

Amyotrophic lateral sclerosis; Biomarkers; MicroRNAs; miR-1249-3p; miR-142-3p

[Indexed for MEDLINE]

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