Survival in high-risk prostate cancer patients is predicted by mir-221, which regulates proliferation, apoptosis and invasion of prostate cancer cells by inhibiting IRF2 and SOCS3
Menée à partir d'échantillons tumoraux prélevés sur deux cohortes de 134 et 89 patients atteints d'un cancer de la prostate à haut risque, puis in vitro et in vivo, cette étude identifie une association entre l'expression du micro-ARN miR-221 et la survie des patients, puis met en évidence des mécanismes par lesquels ce micro-ARN régule la croissance cellulaire, l'apoptose et le processus invasif
A lack of reliably informative biomarkers to distinguish indolent and lethal prostate cancer (PCa) is one reason this disease is overtreated. miR-221 has been suggested as a biomarker in high risk PCa, but there is insufficient evidence of its potential utility. Here we report that miR-221 is an independent predictor for cancer-related death, extending and validating earlier findings. By mechanistic investigations we showed that miR-221 regulates cell growth, invasiveness and apoptosis in PCa at least partially via STAT1/STAT3 mediated activation of the JAK/STAT signalling pathway. miR-221 directly inhibits the expression of SOCS3 and IRF2, two oncogenes that negatively regulate this signalling pathway. miR-221 expression sensitized PCa cells for IFN-γ mediated growth inhibition. Our findings suggest that miR-221 offers a novel prognostic biomarker and therapeutic target in high-risk PCa.
Cancer Research , article en libre accès, 2014