Highlights
- •MicroRNAs were deregulated in the hippocampal tissue of SAMP8 mice.
- •miR-181 levels decreased with aging in the hippocampus tissue.
- •miR-181c directly targeted the 3′-UTR of crmp2 mRNA.
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is usually
accompanied by abnormal gene expression. The 20 to 25 nucleotide (nt) tiny regulators,
known as micro ribonucleic acids (miRNAs), have been found to play important roles
in the etiology and pathogenesis of various biological processes. The purpose of the
current study was to identify the aberrant expression of microRNAs in the hippocampus
of an AD mouse model and to investigate its potential role during the progression
of AD. The results from microarray analysis showed that several miRNAs were deregulated
in the hippocampus tissue of SAMP8 mice compared to SAMR1 mice. Among the deregulated
miRNAs, a significant decrease in miR-181c was validated by quantitative real-time
PCR. Bioinformatic analysis revealed that miR-181c might be involved in the regulation
of axon guidance, MAPK signaling, dorso-ventral axis formation and long-term depression.
Moreover, the results of a luciferase activity assay, western blot analysis and immunofluorescent
staining showed that over-expression of miR-181c targets the 3′-untranslated region
(3′-UTR) of collapsin response mediator protein 2 (crmp2) through its binding sites
and down-regulates crmp2 protein abundance at the post-transcriptional level. Taken
together, these findings suggested that crmp2 is a target of miR-181c and that the
abnormally low expression of miR-181c in the hippocampus of SAMP8 mice could lead
to an increase of the crmp2 protein level in AD mice, which might potentially play
a role in the pathogenesis of Alzheimer's disease.
Keywords
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Article info
Publication history
Published online: May 19, 2016
Accepted:
May 18,
2016
Received in revised form:
May 5,
2016
Received:
February 5,
2016
Identification
Copyright
© 2016 Elsevier B.V. All rights reserved.
