MicroRNA-206: a potential circulating biomarker candidate for amyotrophic lateral sclerosis

PLoS One. 2014 Feb 20;9(2):e89065. doi: 10.1371/journal.pone.0089065. eCollection 2014.

Abstract

Amyotrophic lateral sclerosis (ALS) is a lethal motor neuron disease that progressively debilitates neuronal cells that control voluntary muscle activity. Biomarkers are urgently needed to facilitate ALS diagnosis and prognosis, and as indicators of therapeutic response in clinical trials. microRNAs (miRNAs), small posttranscriptional modifiers of gene expression, are frequently altered in disease conditions. Besides their important regulatory role in variety of biological processes, miRNAs can also be released into the circulation by pathologically affected tissues and display remarkable stability in body fluids. In a mouse model of ALS that expresses mutated human superoxide dismutase 1 (SOD1-G93A) skeletal muscle is one of the tissues affected early by mutant SOD1 toxicity. To find biomarkers for ALS, we studied miRNA alterations from skeletal muscle and plasma of SOD1-G93A mice, and subsequently tested the levels of the affected miRNAs in the serum from human ALS patients. Fast-twitch and slow-twitch muscles from symptomatic SOD1-G93A mice (age 90 days) and their control littermates were first studied using miRNA microarrays and then evaluated with quantitative PCR from five age groups from neonatal to the terminal disease stage (10-120 days). Among those miRNA changed in various age/gender/muscle groups (miR-206, -1, -133a, -133b, -145, -21, -24), miR-206 was the only one consistently altered during the course of the disease pathology. In both sexes, mature miR-206 was increased in fast-twitch muscles preferably affected in the SOD1-G93A model, with highest expression towards the most severely affected animals. Importantly, miR-206 was also increased in the circulation of symptomatic animals and in a group of 12 definite ALS patients tested. We conclude that miR-206 is elevated in the circulation of symptomatic SOD1-G93A mice and possibly in human ALS patients. Although larger scale studies on ALS patients are warranted, miR-206 is a promising candidate biomarker for this motor neuron disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / blood*
  • Amyotrophic Lateral Sclerosis / genetics*
  • Animals
  • Biomarkers / blood
  • Female
  • Gene Expression Regulation
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • MicroRNAs / blood*
  • MicroRNAs / genetics*
  • Middle Aged
  • Muscle Fibers, Fast-Twitch / metabolism
  • Muscle Fibers, Slow-Twitch / metabolism
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase-1

Substances

  • Biomarkers
  • MicroRNAs
  • Mirn206 microRNA, mouse
  • SOD1 protein, human
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1

Grant support

This work was funded by The ALS Association (http://www.alsa.org/, grant S54406), Government of Spain (grant RYC-2011-08363) and University of Zaragoza (grant JIUZ-2012-IO-06). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.