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Genome-wide circulating microRNA expression profiling reveals potential biomarkers for amyotrophic lateral sclerosis.
Neurobiol Aging. 2018 04; 64:123-138.NA

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.

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Authors+Show Affiliations

Matamala JM
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.
Arias-Carrasco R
Center for Genomics and Bioinformatics, Faculty of Sciences, Universidad Mayor, Santiago, Chile.
Sanchez C
Center for Genomics and Bioinformatics, Faculty of Sciences, Universidad Mayor, Santiago, Chile.
Uhrig M
Center for Genomics and Bioinformatics, Faculty of Sciences, Universidad Mayor, Santiago, Chile.
Bargsted L
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.
Matus S
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.
Maracaja-Coutinho V
Center for Genomics and Bioinformatics, Faculty of Sciences, Universidad Mayor, Santiago, Chile.
Abarzua S
Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, Santiago, Chile.
van Zundert B
Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, Santiago, Chile.
Verdugo R
Department of Neurological Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
Manque P
Center for Genomics and Bioinformatics, Faculty of Sciences, Universidad Mayor, Santiago, Chile. Electronic address: patricio.manque@umayor.cl.
Hetz C
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.

MeSH

AdultAgedAmyotrophic Lateral SclerosisAnimalsBiomarkersCirculating MicroRNADisease Models, AnimalFemaleGenome-Wide Association StudyHumansMaleMice, TransgenicTranscriptome

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29458840

Citation

Matamala, José Manuel, et al. "Genome-wide Circulating microRNA Expression Profiling Reveals Potential Biomarkers for Amyotrophic Lateral Sclerosis." Neurobiology of Aging, vol. 64, 2018, pp. 123-138.
Matamala JM, Arias-Carrasco R, Sanchez C, et al. Genome-wide circulating microRNA expression profiling reveals potential biomarkers for amyotrophic lateral sclerosis. Neurobiol Aging. 2018;64:123-138.
Matamala, J. M., Arias-Carrasco, R., Sanchez, C., Uhrig, M., Bargsted, L., Matus, S., Maracaja-Coutinho, V., Abarzua, S., van Zundert, B., Verdugo, R., Manque, P., & Hetz, C. (2018). Genome-wide circulating microRNA expression profiling reveals potential biomarkers for amyotrophic lateral sclerosis. Neurobiology of Aging, 64, 123-138. https://doi.org/10.1016/j.neurobiolaging.2017.12.020
Matamala JM, et al. Genome-wide Circulating microRNA Expression Profiling Reveals Potential Biomarkers for Amyotrophic Lateral Sclerosis. Neurobiol Aging. 2018;64:123-138. PubMed PMID: 29458840.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genome-wide circulating microRNA expression profiling reveals potential biomarkers for amyotrophic lateral sclerosis. AU - Matamala,José Manuel, AU - Arias-Carrasco,Raul, AU - Sanchez,Carolina, AU - Uhrig,Markus, AU - Bargsted,Leslie, AU - Matus,Soledad, AU - Maracaja-Coutinho,Vinicius, AU - Abarzua,Sebastian, AU - van Zundert,Brigitte, AU - Verdugo,Renato, AU - Manque,Patricio, AU - Hetz,Claudio, Y1 - 2017/12/29/ PY - 2017/08/11/received PY - 2017/12/18/revised PY - 2017/12/21/accepted PY - 2018/2/21/entrez PY - 2018/2/21/pubmed PY - 2018/9/28/medline KW - Amyotrophic lateral sclerosis KW - Biomarkers KW - MicroRNAs KW - miR-1249-3p KW - miR-142-3p SP - 123 EP - 138 JF - Neurobiology of aging JO - Neurobiol Aging VL - 64 N2 - 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. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/29458840/Genome_wide_circulating_microRNA_expression_profiling_reveals_potential_biomarkers_for_amyotrophic_lateral_sclerosis_ DB - PRIME DP - Unbound Medicine ER -