A miRNA signature in leukocytes from sporadic amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a progressive and seriously disabling adult-onset neurological disease. Accumulating evidence indicates that various miRNAs, expressed in a spatially and temporally controlled manner in the brain, play a key role in neuronal development. In addition, misregulation of microRNAs contributes to some mental disorders and neurodegeneration diseases. Here, we analyzed the expression profiles of 911 human miRNAs using microarray technology in leukocytes, the most readily available human tissue cells, obtained from 8 patients affected by sporadic amyotrophic lateral sclerosis (sALS) and 12 healthy controls. An independent group of 14 sALS patients and 14 controls was used for validation by TaqMan real-time polymerase chain reaction assay. We identified 8 miRNAs that were significantly up- or downregulated in sALS patients as compared to healthy controls. The significant variations in miRNAs profiles detected in leukocytes have been related to miRNAs predominantly expressed in the nervous system. One of these miRNAs, miR-338-3p, has previously been shown to be de-regulated in ALS brains. This study, for the first time, detected specific microRNAs disease-related changes at an earlier stage of sALS. We suggest that miRNAs profiles found in the peripheral blood leukocytes from sALS patients can be relevant to understand the pathogenesis of sALS and/or used as biomarkers of the disease.
Department of Life Sciences, University of Naples II, Via Vivaldi 43, 81100 Caserta, Italy. bruna.defelice@unina2.it
Bruna
B
De Felice
Marco
M
Guida
Maurizio
M
Guida
Cinzia
C
Coppola
Giovanna
G
De Mieri
Roberto
R
Cotrufo
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood*; D027342:Excitatory Amino Acid Transporter 2; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D050491:Glutamate Plasma Membrane Transport Proteins / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction
D015415:Biomarkers; D027342:Excitatory Amino Acid Transporter 2; D050491:Glutamate Plasma Membrane Transport Proteins; C532050:MIRN338 microRNA, human; D035683:MicroRNAs; C493397:SLC1A2 protein, human