A number of studies have shown that increased APP levels, resulting from either a genomic locus duplication or alteration in APP regulatory sequences, can lead to development of early-onset dementias, including Alzheimer's disease (AD). Therefore, understanding how APP levels are regulated could provide valuable insight into the genetic basis of AD and illuminate novel therapeutic avenues for AD. Here we test the hypothesis that APP protein levels can be regulated by miRNAs, evolutionarily conserved small noncoding RNA molecules that play an important role in regulating gene expression. Utilizing human cell lines, we demonstrate that miRNAs hsa-mir-106a and hsa-mir-520c bind to their predicted target sequences in the APP 3'UTR and negatively regulate reporter gene expression. Over-expression of these miRNAs, but not control miRNAs, results in translational repression of APP mRNA and significantly reduces APP protein levels. These results are the first to demonstrate that levels of human APP can be regulated by miRNAs.
Jack Timothy Rogers - Massachusetts General Hospital
Jeremy C Lee - University of California, Santa Cruz
Aleister J Saunders - Drexel University
Publication Details
Molecular neurodegeneration, v 3(1), 10
Publisher
BioMed Central
Number of pages
6
Grant note
Commonwealth of Pennsylvania
Drexel University
R21NS48227 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
Resource Type
Journal article
Language
English
Academic Unit
Biology
Web of Science ID
WOS:000265633200001
Scopus ID
2-s2.0-51149091628
Other Identifier
991021448057904721
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