MicroRNA-424 impairs ubiquitination to activate STAT3 and promote prostate tumor progression.

Détails

ID Serval
serval:BIB_CCE872B9EF32
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
MicroRNA-424 impairs ubiquitination to activate STAT3 and promote prostate tumor progression.
Périodique
The Journal of clinical investigation
Auteur(s)
Dallavalle C., Albino D., Civenni G., Merulla J., Ostano P., Mello-Grand M., Rossi S., Losa M., D'Ambrosio G., Sessa F., Thalmann G.N., Garcia-Escudero R., Zitella A., Chiorino G., Catapano C.V., Carbone G.M.
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Statut éditorial
Publié
Date de publication
01/12/2016
Peer-reviewed
Oui
Volume
126
Numéro
12
Pages
4585-4602
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Mutations and deletions in components of ubiquitin ligase complexes that lead to alterations in protein turnover are important mechanisms in driving tumorigenesis. Here we describe an alternative mechanism involving upregulation of the microRNA miR-424 that leads to impaired ubiquitination and degradation of oncogenic transcription factors in prostate cancers. We found that miR-424 targets the E3 ubiquitin ligase COP1 and identified STAT3 as a key substrate of COP1 in promoting tumorigenic and cancer stem-like properties in prostate epithelial cells. Altered protein turnover due to impaired COP1 function led to accumulation and enhanced basal and cytokine-induced activity of STAT3. We further determined that loss of the ETS factor ESE3/EHF is the initial event that triggers the deregulation of the miR-424/COP1/STAT3 axis. COP1 silencing and STAT3 activation were effectively reverted by blocking of miR-424, suggesting a possible strategy to attack this key node of tumorigenesis in ESE3/EHF-deficient tumors. These results establish miR-424 as an oncogenic effector linked to noncanonical activation of STAT3 and as a potential therapeutic target.

Pubmed
Web of science
Open Access
Oui
Création de la notice
16/01/2017 18:46
Dernière modification de la notice
20/08/2019 16:47
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