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
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
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
UR - http://www.scopus.com/inward/record.url?scp=85041397888&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2017.12.020
DO - 10.1016/j.neurobiolaging.2017.12.020
M3 - Article
AN - SCOPUS:85041397888
SN - 0197-4580
VL - 64
SP - 123
EP - 138
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -