A New study published in The Journal of Clinical Investigation by Dr. Carbone group

news on 7 Nov , 2016

A new study has been published by the group led by Dr. Giuseppina Carbone at the Institute of Oncology Research (IOR). The article entitled “MicroRNA-424 impairs ubiquitination to activate STAT3 and promote prostate tumor progression” appears today in The Journal of Clinical Investigation.

Mutations and deletions of components of ubiquitin ligase complexes leading to altered protein turnover are important mechanisms driving tumorigenesis. The paper from Dr. Carbone’s group describes an alternative mechanism involving miR-424 up-regulation and leading to impaired ubiquitination and degradation of oncogenic transcription factors in prostate tumors. They found that miR-424 targets the E3 ubiquitin ligase COP1 and identify STAT3 as a key substrate of COP1 promoting tumorigenic and cancer stem-like properties in prostate epithelial cells. Altered protein turnover due to impaired COP1 function leads to accumulation and enhanced basal and cytokine-induced activity of STAT3. Loss of the transcription factor ESE3/EHF is the initial event triggering the deregulation of the miR424/COP1/STAT3 axis. Inhibition of miR-424 reduced tumor initiating and metastatic capability in prostate cancer cells and resulted in inhibition of STAT3, suggesting that strategies focused on ablating this microRNA may be effective in treating certain types of prostate cancers.

Reference

Dallavalle C, Albino D, Civenni G, Merulla J, Ostano P, Mello-Grand M, Rossi S, Losa M, D’Ambrosio G, Sessa F, Thalmann G, Garcia-Escudero R, Zitella A, Chiorino G, Catapano CV, Carbone GM. MicroRNA-424 impairs ubiquitination to activate STAT3 and promote prostate tumor progression. Journal of Clinical Investigation, 2016 Published on line November 7, 2016