Micrornas as predictive and therapeutic tools in prostate cancer and bone metastasis

Abstract

Prostate cancer (PCa) is one of the leading causes of cancer-related death in men. Despite significant advances in prostate cancer diagnosis and management, validation of new biomarkers able to distinguish among early, androgen-insensitive and metastatic tumors are still necessary to guide therapeutic decisions and to improve patient prognosis. Since c-Met is considered to have a role in PCa progression towards metastatic stage, we investigated the effect of this receptor in microRNA (miR) expression profiles of several prostate cancer cell lines and a cancer-stem cell population (PCSC-1) isolated from fresh surgery specimen. We focused on miR-130b which is considered an oncomiR able to confer tumorigenic and stemness properties to the cells. Expression of miR-130b in prostate cancer cell lines is directly correlated with c-Met and its forced expression in LnCaP cells led to a significant down-regulation of AR and an increase of srivival genes, such as Bcl-2 and Mcl-1, and metastasis-associated markers such as IL-11 and CXCR-4. As a consequence, these cells were able to overcome in vitro inhibitory effects of Casodex and to grow orthotopically and form distant metastasis in vivo in immune-compromised mice, as compared with their control. Finally, we analyzed expression of miR-130b in a large dataset of patients and we found a strong correlation between miR-130b levels and tumor recurrence and metastasis. Taken together, our observations provide insights to the importance of miR-130b, that could be a novel biomarker to predict the prognosis and progression of patients with prostate cancer.