The miRNome of Alzheimer's disease: consistent downregulation of the miR-132/212 cluster.
MicroRNAs (miRNAs) are small noncoding RNA molecules, with essential functions in RNA silencing and post-transcriptional regulation of gene expression. miRNAs appear to regulate the development and function of the nervous system. Alterations of miRNA expression have been associated with Alzheimer's disease (AD). To characterize the AD miRNA signature, we examined genome-wide miRNA and mRNA expression patterns in the temporal cortex of AD and control samples. We validated our miRNA results by semiquantitative real-time polymerase chain reaction (PCR) in independent prefrontal cortex. Furthermore, we separated gray and white matter brain sections to identify the cellular origin of the altered miRNA expression. We observed genome-wide downregulation of hsa-miR-132-3p and hsa-miR-212-3p in AD with a stronger decrease in gray matter AD samples. We further identified 10 differently expressed transcripts achieving genome-wide levels of significance. Significantly deregulated miRNAs and mRNAs were correlated and examined for potential binding sites (in silico). This miRNome-wide study in AD provides supportive evidence and corroborates an important contribution of miR-132/212 and corresponding target mRNAs to the pathogenesis of AD.
Department of Psychiatry and Psychotherapy, Neurobiological Laboratory, Saarland University, Homburg, Germany. Electronic address: sabrina.pichler@uks.eu.
Sabrina
S
Pichler
Department of Psychiatry and Psychotherapy, Neurobiological Laboratory, Saarland University, Homburg, Germany; Luxembourg Centre For Systems Biomedicine (LCSB), University of Luxembourg, Esch-Belval, Luxembourg.
Wei
W
Gu
Department of Psychiatry and Psychotherapy, Neurobiological Laboratory, Saarland University, Homburg, Germany.
Daniela
D
Hartl
Department of Psychiatry and Psychotherapy, Neurobiological Laboratory, Saarland University, Homburg, Germany.
Gilles
G
Gasparoni
Department of Human Genetics, Saarland University, Homburg, Germany.
Petra
P
Leidinger
Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.
Andreas
A
Keller
Department of Human Genetics, Saarland University, Homburg, Germany.
Eckart
E
Meese
Department of Psychiatry and Psychotherapy, Neurobiological Laboratory, Saarland University, Homburg, Germany.
Manuel
M
Mayhaus
AXA Research Fund & UPMC Chair, Paris, France; Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A) & Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris, France.
Harald
H
Hampel
Department of Psychiatry and Psychotherapy, Neurobiological Laboratory, Saarland University, Homburg, Germany; Department of Psychiatry and Psychotherapy, Saarland University Hospital, Homburg, Germany.
Matthias
M
Riemenschneider
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D001665:Binding Sites; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D055106:Genome-Wide Association Study; D066128:Gray Matter / Q000378:metabolism; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family / Q000235:genetics*
C547077:MIRN132 microRNA, human; C551411:MIRN212 microRNA, human; D035683:MicroRNAs
Alzheimer's disease; Hsa-miR-132; Hsa-miR-212; Human cortical brain tissue; mRNA; microRNA