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| Status |
Public on Mar 19, 2018 |
| Title |
IGF2BP1 enhances an aggressive tumor cell phenotype by impairing miRNA-directed downregulation of oncogenic factors [small RNA] |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
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| Summary |
The oncofetal IGF2 mRNA binding protein (IGF2BP) family modulates tumor cell properties but IGF2BP paralogue-specific roles remain poorly understood. We demonstrate that phenotypic roles of IGF2BPs vary in a cancer cell-dependent manner. However, only IGF2BP1 shows oncogenic potential in all cancer cells analyzed. Consistently, only IGF2BP1 expression is associated with poor prognosis in ovarian carcinoma and promotes all oncogenic properties analyzed in ovarian cancer-derived tumor cells. Despite a substantial overlap of candidate target mRNAs of IGF2BP paralogues proposed by CLIP analyses, the paralogue-specific depletion of IGF2BPs induces strikingly distinct deregulation of mRNA abundance. Transcripts decreased by IGF2BP1 depletion or knockout are enriched for IGF2BP1- as well as AGO-CLIP hits conserved in distinct cell lines, are prone to targeting by highly abundant miRNAs and comprise significantly longer 3’UTRs. The downregulation of target mRNAs observed upon IGF2BP1 depletion is abrogated when miRNAs are expressed at low levels or depleted by DICER/DROSHA knockdown. Strikingly, the depletion of 10 randomly selected miRNA-prone target mRNAs impairs at least one analyzed IGF2BP1-modulated tumor cell property. These findings indicate that IGF2BPs serve distinct roles in cancer-derived cells and suggest that IGF2BP1’s main role is the post-transcriptional, miRNome-dependent enhancement of factors promoting oncogenic tumor cell properties.
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| Overall design |
small RNA-Seq of ES-2 cells transfected with either control siRNAs (siC) or siRNAs directed against IGF2BP1, IGF2BP2 or IGF2BP3. Two or three replicates per condition.
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| Contributor(s) |
Müller S, Bley N, Glaß M, Busch B, Rousseau V, Misiak D, Fuchs T, Lederer M, Hüttelmaier S |
| Citation(s) |
29660014 |
| Submission date |
Jan 19, 2018 |
| Last update date |
Dec 28, 2018 |
| Contact name |
Markus Glaß |
| E-mail(s) |
markus.glass@medizin.uni-halle.de
|
| Organization name |
Martin Luther University Halle-Wittenberg
|
| Department |
Institute of Molecular Medicine
|
| Lab |
Huettelmaier Lab
|
| Street address |
Kurt-Mothes-Str. 3a
|
| City |
Halle |
| ZIP/Postal code |
06120 |
| Country |
Germany |
| |
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| Platforms (1) |
| GPL15456 |
Illumina HiScanSQ (Homo sapiens) |
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| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE109605 |
IGF2BP1 enhances an aggressive tumor cell phenotype by impairing miRNA-directed downregulation of oncogenic factors |
|
| Relations |
| BioProject |
PRJNA430865 |
| SRA |
SRP131144 |
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