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

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)123-138
Number of pages16
JournalNeurobiology of Aging
Volume64
DOIs
Publication statusPublished - 1 Apr 2018

Keywords

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

ASJC Scopus subject areas

  • General Neuroscience
  • Ageing
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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