Accession ID: MIRT000430 [miRNA, hsa-miR-101 ::
APP, target gene]
| miRNA name | hsa-miR-101 |
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| Gene Symbol | APP LinkOut: [ Entrez Gene | BioGPS | Wikipedia | iHop ] |
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| Synonyms | AAA, ABETA, ABPP, AD1, APPI, CTFgamma, CVAP, PN2 |
| Description | amyloid beta (A4) precursor protein |
| Transcript | NM_000484 LinkOut: [ RefSeq ] |
| Other Transcripts | NM_001136129, NM_001136130, NM_201413, NM_201414 |
| Expression | LinkOut: [ BioGPS ] |
| KEGG Pathway |
hsa05010 Alzheimer's disease - Homo sapiens (human) |
| Putative miRNA Targets on APP | LinkOut: [ TargetScan 5.1 | MicroCosm | miRNAMap 2.0 ] |
| 3'UTR of APP (miRNA target sites are highlighted) |
>APP|NM_000484|3'UTR 1 TAGACCCCCGCCACAGCAGCCTCTGAAGTTGGACAGCAAAACCATTGCTTCACTACCCATCGGTGTCCATTTATAGAATA 81 ATGTGGGAAGAAACAAACCCGTTTTATGATTTACTCATTATCGCCTTTTGACAGCTGTGCTGTAACACAAGTAGATGCCT 161 GAACTTGAATTAATCCACACATCAGTAATGTATTCTATCTCTCTTTACATTTTGGTCTCTATACTACATTATTAATGGGT 241 TTTGTGTACTGTAAAGAATTTAGCTGTATCAAACTAGTGCATGAATAGATTCTCTCCTGATTATTTATCACATAGCCCCT 321 TAGCCAGTTGTATATTATTCTTGTGGTTTGTGACCCAATTAAGTCCTACTTTACATATGCTTTAAGAATCGATGGGGGAT 401 GCTTCATGTGAACGTGGGAGTTCAGCTGCTTCTCTTGCCTAAGTATTCCTTTCCTGATCACTATGCATTTTAAAGTTAAA 481 CATTTTTAAGTATTTCAGATGCTTTAGAGAGATTTTTTTTCCATGACTGCATTTTACTGTACAGATTGCTGCTTCTGCTA 561 TATTTGTGATATAGGAATTAAGAGGATACACACGTTTGTTTCTTCGTGCCTGTTTTATGTGCACACATTAGGCATTGAGA 641 CTTCAAGCTTTTCTTTTTTTGTCCACGTATCTTTGGGTCTTTGATAAAGAAAAGAATCCCTGTTCATTGTAAGCACTTTT 721 ACGGGGCGGGTGGGGAGGGGTGCTCTGCTGGTCTTCAATTACCAAGAATTCTCCAAAACAATTTTCTGCAGGATGATTGT 801 ACAGAATCATTGCTTATGACATGATCGCTTTCTACACTGTATTACATAAATAAATTAAATAAAATAACCCCGGGCAAGAC 881 TTTTCTTTGAAGGATGACTACAGACATTAAATAATCGAAGTAATTTTGGGTGGGGAGAAGAGGCAGATTCAATTTTCTTT 961 AACCAGTCTGAAGTTTCATTTATGATACAAAAGAAGATGAAAATGGAAGTGGCAATATAAGGGGATGAGGAAGGCATGCC 1041 TGGACAAACCCTTCTTTTAAGATGTGTCTTCAATTTGTATAAAATGGTGTTTTCATGTAAATAAATACATTCTTGGAGGA 1121 GCAAAAAAAAAAAAAAAA Target sites Provided by authors Predicted by miRanda |
| miRNA:Target | hsa-miR-101 :: APP [ Functional MTI ] | ||||||
|---|---|---|---|---|---|---|---|
| Validation Method | qRT-PCR , Luciferase reporter assay , Western blot | ||||||
| Conditions | HEK293T | ||||||
| Location of target site | 3'UTR | ||||||
| Tools used in this research | TargetScan, PicTar | ||||||
| Original Description (Extracted from the article) | ... In addition, miR-101 contributed to the regulation of APP in response to the proinflammatory cytokine interleukin-1β (IL-lβ). Thus, miR-101 is a negative regulator of APP expression and affects the accumulation of Aβ, suggesting a possible role for miR-101 in neuropathological conditions//Among microRNAs potentially targeting the APP 3’UTR, miR-101 is a microRNA with two putative REs within the APP 3’UTR and is also expressed in adult hippocampal tissue. Expression of miR-101 and APP both in embryonic primary hippocampal cell cultures and in postnatal rat hippocampal tissues further support the hypothesis that miR-101 is a repressor of hippocampal APP expression.// These data suggest that modification of the site 1 RE of the APP 3’UTR is sufficient to block the inhibitory function of miR-101 (Fig. 4B). Thus, miR-101 functionally interacts with the APP 3’UTR. ... - Vilardo, E. Barbato, C. Ciotti, M. Cogoni, et al., 2010, J Biol Chem. |
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| miRNA-target interactions (Provided by authors) |
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| Article |
- Vilardo, E.
Barbato, C.
Ciotti, M.
Cogoni, et al. - J Biol Chem, 2010
The amyloid precursor protein (APP) and its proteolytic product amyloid beta (Abeta) are associated with both familial and sporadic forms of Alzheimer disease (AD). Aberrant expression and function of microRNAs has been observed in AD. Here, we show that in rat hippocampal neurons cultured in vitro, the down-regulation of Argonaute-2, a key component of the RNA-induced silencing complex, produced an increase in APP levels. Using site-directed mutagenesis, a microRNA responsive element (RE) for miR-101 was identified in the 3'-untranslated region (UTR) of APP. The inhibition of endogenous miR-101 increased APP levels, whereas lentiviral-mediated miR-101 overexpression significantly reduced APP and Abeta load in hippocampal neurons. In addition, miR-101 contributed to the regulation of APP in response to the proinflammatory cytokine interleukin-1beta (IL-lbeta). Thus, miR-101 is a negative regulator of APP expression and affects the accumulation of Abeta, suggesting a possible role for miR-101 in neuropathological conditions.
LinkOut: [PMID: 20395292]
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| miRNA:Target | hsa-miR-101 :: APP [ Functional MTI ] |
|---|---|
| Validation Method | Luciferase reporter assay , qRT-PCR , Western blot |
| Conditions | HeLa, HEK293T, U373, SK-N-SH, PC12 |
| Location of target site | 3'UTR |
| Tools used in this research | miRanda, PicTar, PITA, TargetScan |
| Original Description (Extracted from the article) | ... Endogenous miR-101 regulates expression of APP in human cells via a specific site located within its 3'UTR ... - Long, J. M. Lahiri, D. K., 2011, Biochemical and Biophysical Research Communications. |
| Article |
- Long, J. M.
Lahiri, D. K. - Biochemical and Biophysical Research Communications, 2011
The full repertoire of regulatory interactions utilized by human cells to control expression of amyloid-beta precursor protein (APP) is still undefined. We investigated here the contribution of microRNA (miRNA) to this regulatory network. Several bioinformatic algorithms predicted miR-101 target sites within the APP 3'-untranslated region (3'-UTR). Using reporter assays, we confirmed that, in human cell cultures, miR-101 significantly reduced the expression of a reporter under control of APP 3'-UTR. Mutation of predicted site 1, but not site 2, eliminated this reporter response. Delivery of miR-101 directly to human HeLa cells significantly reduced APP levels and this effect was eliminated by co-transfection with a miR-101 antisense inhibitor. Delivery of a specific target protector designed to blockade the interaction between miR-101 and its functional target site within APP 3'-UTR enhanced APP levels in HeLa. Therefore, endogenous miR-101 regulates expression of APP in human cells via a specific site located within its 3'-UTR. Finally, we demonstrate that, across a series of human cell lines, highest expression of miR-101 levels was observed in model NT2 neurons.
LinkOut: [PMID: 21172309]
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