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| Status |
Public on Aug 28, 2010 |
| Title |
TEL-AML1 regulation of survivin and apoptosis via miRNA-494 and miRNA-320a |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by genome tiling array
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| Summary |
There is increasing evidence that microRNA and transcription factors interact in an instructive fashion in normal and malignant hematopoiesis. We explored the impact of TEL-AML1 (ETV6-RUNX1), the most common fusion protein in childhood leukemia, on miRNA expression and the leukemic phenotype. Using RNA interference, miRNA expression arrays, and quantitative PCR, we identified miRNA-494 and miRNA-320a to be upregulated upon TEL-AML1 silencing independently of TEL expression. Chromatin immunoprecipitation analysis identified miRNA-494 as a direct miRNA target of the fusion protein TEL-AML1. Using bioinformatic analysis as well as functional luciferase experiments we demonstrate that survivin is a target of the two miRNAs. MiRNA-494 and -320a were introduced to the cells by transfection and survivin expression determined by western blot analysis. These miRNAs blocked survivin expression and resulted in apoptosis in a similar manner as TEL-AML1 silencing by itself; this silencing was also shown to be DICER-dependent. MiRNAs-494 and -320a are expressed at lower levels in TEL-AML1+ leukemias compared to immunophenotype-matched non-TEL-AML1 ALL subtypes, and within TEL-AML1+ leukemias their expression is correlated to survivin levels. In summary our data suggest that TEL-AML1 might exert its anti-apoptotic action at least in part by suppressing miRNA-494 and miRNA-320a, lowering their expression causing enhanced survivin expression.
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| Overall design |
DNAs from REH cells were pulled down using ChIP antibodies to TEL and hybridized to microRNA promoter tiling arrays.
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| Contributor(s) |
Wiemels JL |
| Citation(s) |
20807887 |
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| Submission date |
Aug 27, 2010 |
| Last update date |
Mar 22, 2012 |
| Contact name |
Joseph Leo Wiemels |
| E-mail(s) |
[email protected]
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| Phone |
415 514-0577
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| Fax |
415 502-7411
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| Organization name |
UCSF
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| Lab |
Epidemiology
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| Street address |
1450 3rd Street, MC 0520
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94158 |
| Country |
USA |
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| Platforms (1) |
| GPL10861 |
Custom NimbleGen human microRNA promoter array [071121_HG18_ncRNA] |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA130657 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE23842_RAW.tar |
52.0 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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