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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 31, 2017 |
| Title |
Gene expression profiling of noncancerous prostate epithelial cells (RWPE-1) following pre-miR-424 transfection |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
MicroRNAs (miRNAs) play important roles in cell differentiation and self-renewal controlling post-transcriptional processing of mRNAs and attenuating production of the encoded proteins. Here, we unveil a novel oncogenic pathway leading to activation of STAT3 signaling through miRNA-mediated silencing of the E3 ubiquitin ligase COP1. miRNA profiling showed that miR-424 was upregulated in prostate cancer compared to normal prostate and specifically associated with reduced level of the ETS factor ESE3/EHF in an aggressive subgroup of tumors. MiR-424 was significantly elevated also in other epithelial cancers and amplified in 1-3% of various cancers. In normal prostate epithelial cells miR-424 was repressed by ESE3/EHF and when upregulated promoted oncogenic and cancer stem cell (CSC) properties. Conversely, ablation of miR-424 in metastatic prostate cancer cells reduced CSC self-renewal and prevented in vivo tumour initiation and metastatic spread. miR-424 targeted the 3' UTR of COP1 mRNA and reduced COP1 protein level. COP1 induced STAT3 ubiquitylation and degradation by the ubiquitin-proteasome system (UPS). Therefore, reduced levels of COP1 in prostate cancer cells, resulted in accumulation and increased STAT3 signaling. COP1 knockdown and over-expression phenocopied the effects of miR-424 deregulation on oncogenic phenotypes and STAT3 signalling, while STAT3 knockdown prevented the transforming effects of miR-424. Consistently, expression of EHF/ESE3 and RFWD2/COP1 were highly correlated in human prostate cancers and other epithelial tumors. Furthermore, miR-424 induced genes were enriched of STAT3 targets, converged with those induced by COP1 loss in mouse embryos and were associated with adverse prognosis in prostate and other epithelial cancers. In primary prostate tumours, low COP1 and high STAT3 protein level were also significantly associated and predictive of biochemical relapse. Collectively, this study reveals a novel miRNA-activated oncogenic axis in prostate cancer. Targeting miR-424 or miR-424 dependent pathways may represent a unique approach to attack a key node in tumorigenesis.
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| Overall design |
Investigation of gene expression profiles of noncancerous prostate epithelial cells (RWPE-1) following pre-miR-424 transfection vs. control. Two technical replicates (dye swaps) were performed.
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| Contributor(s) |
Dallavalle C, Albino D, Civenni G, Ostano P, Mello-Grand M, Thalmann G, Garcia-Escudero R, Chiorino G, Catapano CV, Carbone GM |
| Citation(s) |
27384993 |
| Submission date |
Aug 07, 2014 |
| Last update date |
Apr 02, 2018 |
| Contact name |
Paola Ostano |
| Organization name |
Fondazione Edo ed Elvo Tempia
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| Street address |
via Malta 3
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| City |
Biella |
| ZIP/Postal code |
13900 |
| Country |
Italy |
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| Platforms (1) |
| GPL14550 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Probe Name Version) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE60371 |
miR-424 induces COP1 silencing and STAT3 activation in prostate cancer: a novel miRNA-dependent axis driving tumor progression |
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| Relations |
| BioProject |
PRJNA257736 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE60201_RAW.tar |
12.0 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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