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Series GSE60117 Query DataSets for GSE60117
Status Public on Dec 31, 2017
Title miRNA expression profiling of prostate cancer (PCa) and normal prostatic samples
Organism Homo sapiens
Experiment type Non-coding RNA profiling by array
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.
Overall design 21 samples from normal prostate and 56 from prostate cancer were analyzed for miRNA expression profiling.
Contributor(s) Chiorino G, Mello-Grand M, Ostano P, Singh V
Citation(s) 27384993
Submission date Aug 05, 2014
Last update date Dec 18, 2019
Contact name Paola Ostano
Organization name Fondazione Edo ed Elvo Tempia
Street address via Malta 3
City Biella
ZIP/Postal code 13900
Country Italy
Platforms (1)
GPL13264 Agilent-021827 Human miRNA Microarray (V3) (Probe Name version)
Samples (77)
GSM1465192 Normal_BA27apr05
GSM1465193 Normal_FI01giu05
GSM1465194 Normal_GA25mag05
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
BioProject PRJNA257727

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE60117_RAW.tar 155.8 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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