Open Access Open Badges Short report

MicroRNAs can regulate human APP levels

Neha Patel1, David Hoang1, Nathan Miller1, Sara Ansaloni1, Qihong Huang2, Jack T Rogers3, Jeremy C Lee4 and Aleister J Saunders15*

Author Affiliations

1 Department of Bioscience & Biotechnology, Drexel University, Philadelphia, PA, USA

2 Wistar Institute, Philadelphia, PA, USA

3 Neurochemistry Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

4 Department of Molecular, Cell, & Developmental Biology, University of California, Santa Cruz, CA, USA

5 Departments of Biochemistry & Molecular Biology and Neurobiology & Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA

For all author emails, please log on.

Molecular Neurodegeneration 2008, 3:10  doi:10.1186/1750-1326-3-10

Published: 6 August 2008


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.