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

José Manuel Matamala, Raul Arias-Carrasco, Carolina Sanchez, Markus Uhrig, Leslie Bargsted, Soledad Matus, Vinicius Maracaja-Coutinho, Sebastian Abarzua, Brigitte van Zundert, Renato Verdugo, Patricio Manque, Claudio Hetz

Resultado de la investigación: Article

7 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Páginas (desde-hasta)123-138
Número de páginas16
PublicaciónNeurobiology of Aging
Volumen64
DOI
EstadoPublished - 1 abr 2018

Huella dactilar

Amyotrophic Lateral Sclerosis
MicroRNAs
Biomarkers
Genome
Heat-Shock Proteins
Computational Biology
Serum
Transgenic Mice
Real-Time Polymerase Chain Reaction
RNA
Mutation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Ageing
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Citar esto

Matamala, José Manuel ; Arias-Carrasco, Raul ; Sanchez, Carolina ; Uhrig, Markus ; Bargsted, Leslie ; Matus, Soledad ; Maracaja-Coutinho, Vinicius ; Abarzua, Sebastian ; van Zundert, Brigitte ; Verdugo, Renato ; Manque, Patricio ; Hetz, Claudio. / Genome-wide circulating microRNA expression profiling reveals potential biomarkers for amyotrophic lateral sclerosis. En: Neurobiology of Aging. 2018 ; Vol. 64. pp. 123-138.
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title = "Genome-wide circulating microRNA expression profiling reveals potential biomarkers for amyotrophic lateral sclerosis",
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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Matamala, JM, 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, vol. 64, pp. 123-138. https://doi.org/10.1016/j.neurobiolaging.2017.12.020

Genome-wide circulating microRNA expression profiling reveals potential biomarkers for amyotrophic lateral sclerosis. / Matamala, José Manuel; Arias-Carrasco, Raul; Sanchez, Carolina; Uhrig, Markus; Bargsted, Leslie; Matus, Soledad; Maracaja-Coutinho, Vinicius; Abarzua, Sebastian; van Zundert, Brigitte; Verdugo, Renato; Manque, Patricio; Hetz, Claudio.

En: Neurobiology of Aging, Vol. 64, 01.04.2018, p. 123-138.

Resultado de la investigación: Article

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

PY - 2018/4/1

Y1 - 2018/4/1

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.

AB - 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.

KW - Amyotrophic lateral sclerosis

KW - Biomarkers

KW - MicroRNAs

KW - miR-1249-3p

KW - miR-142-3p

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