MicroRNA-29b Suppresses Prostate Cancer Metastasis by Regulating Epithelial-Mesenchymal Transition Signaling
Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude met en évidence le rôle joué par le micro-ARN29b dans la régulation de la voie de signalisation de la transition épithélio-mésenchymateuse et le processus métastatique
Prostate cancer remains the second leading cause of cancer deaths among American men. Earlier diagnosis increases survival rate in patients; however, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment are necessary for inhibiting prostate cancer disease progression. Here, we have shown that microRNA-29b (miR-29b) expression was lower in prostate cancer cells (PC3 and LNCaP) as compared to immortalized prostate epithelial cells. Between these two prostate cancer cell lines, metastatic prostate cancer PC3 cells displayed lower expression of miR-29b. We also observed a significant downregulation of miR-29b expression in human prostate cancer tissues as compared to patient-matched non-tumor tissues. PC3 cells ectopically expressing miR-29b inhibited wound healing, invasiveness, and failed to colonize in the lungs and liver of SCID mice after intravenous injection, while PC3 cells expressing a control miRNA displayed metastasis. Epithelial cell marker E-cadherin expression was enhanced miR-29b transfected in prostate cancer cells as compared to cells expressing control miRNA. On the other hand, N-Cadherin, Twist and Snail expression were downregulated in PC3 cells expressing miR-29b. Together these results suggested that miR-29b acts as an anti-metastatic miRNA for prostate cancer cells at multiple steps in a metastatic cascade. Therefore, miR-29b could be a potentially new attractive target for therapeutic intervention in prostate cancer.
http://mct.aacrjournals.org/content/early/2012/03/06/1535-7163.MCT-12-0100.abstract