MicroRNAs can regulate human APP levels
<p>Abstract</p> <p>A number of studies have shown that increased APP levels, resulting from either a genomic locus duplication or alteration in <it>APP </it>regulatory sequences, can lead to development of early-onset dementias, including Alzheimer's disease (AD)....
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2008-08-01
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| Series: | Molecular Neurodegeneration |
| Online Access: | http://www.molecularneurodegeneration.com/content/3/1/10 |
| _version_ | 1811250249510944768 |
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| author | Rogers Jack T Huang Qihong Ansaloni Sara Miller Nathan Hoang David Patel Neha Lee Jeremy C Saunders Aleister J |
| author_facet | Rogers Jack T Huang Qihong Ansaloni Sara Miller Nathan Hoang David Patel Neha Lee Jeremy C Saunders Aleister J |
| author_sort | Rogers Jack T |
| collection | DOAJ |
| description | <p>Abstract</p> <p>A number of studies have shown that increased APP levels, resulting from either a genomic locus duplication or alteration in <it>APP </it>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 <it>APP </it>3'UTR and negatively regulate reporter gene expression. Over-expression of these miRNAs, but not control miRNAs, results in translational repression of <it>APP </it>mRNA and significantly reduces APP protein levels. These results are the first to demonstrate that levels of human APP can be regulated by miRNAs.</p> |
| first_indexed | 2024-04-12T16:01:51Z |
| format | Article |
| id | doaj.art-b943201957854becacd15a38e4c7c6fc |
| institution | Directory Open Access Journal |
| issn | 1750-1326 |
| language | English |
| last_indexed | 2024-04-12T16:01:51Z |
| publishDate | 2008-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Neurodegeneration |
| spelling | doaj.art-b943201957854becacd15a38e4c7c6fc2022-12-22T03:26:11ZengBMCMolecular Neurodegeneration1750-13262008-08-01311010.1186/1750-1326-3-10MicroRNAs can regulate human APP levelsRogers Jack THuang QihongAnsaloni SaraMiller NathanHoang DavidPatel NehaLee Jeremy CSaunders Aleister J<p>Abstract</p> <p>A number of studies have shown that increased APP levels, resulting from either a genomic locus duplication or alteration in <it>APP </it>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 <it>APP </it>3'UTR and negatively regulate reporter gene expression. Over-expression of these miRNAs, but not control miRNAs, results in translational repression of <it>APP </it>mRNA and significantly reduces APP protein levels. These results are the first to demonstrate that levels of human APP can be regulated by miRNAs.</p>http://www.molecularneurodegeneration.com/content/3/1/10 |
| spellingShingle | Rogers Jack T Huang Qihong Ansaloni Sara Miller Nathan Hoang David Patel Neha Lee Jeremy C Saunders Aleister J MicroRNAs can regulate human APP levels Molecular Neurodegeneration |
| title | MicroRNAs can regulate human APP levels |
| title_full | MicroRNAs can regulate human APP levels |
| title_fullStr | MicroRNAs can regulate human APP levels |
| title_full_unstemmed | MicroRNAs can regulate human APP levels |
| title_short | MicroRNAs can regulate human APP levels |
| title_sort | micrornas can regulate human app levels |
| url | http://www.molecularneurodegeneration.com/content/3/1/10 |
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