Dysregulation of the miR-1825/TSC2/mTOR Axis Contributes to Prostate Cancer Aggressiveness.

Abstract

Prostate cancer (PCa) is the second most widespread cancer affecting solid tumor in men and the fifth most widespread cause of cancer-associated mortality in men. Research into the underlying molecular mechanisms of PCa is an urgent need to develop better therapeutic strategies and reveal new molecular targets for therapeutic intervention. In this study, we proposed to investigate the functional significance of miR-1825 in driving the malignant characteristics of PCa cells in relation to the TSC2/mTOR axis. We primitively examined the effects of miR-1825 mimic/inhibitor on cell viability, cell motility, and clonogenic ability of DU145, LNCaP, and PC3 PCa cells. Subsequently, we investigated the relationship between miR-1825 expression and the TSC2/mTOR signaling pathway through integrated in vitro and in silico approaches. Overexpression of miR-1825 increasingly suppressed TSC2 expression at both the mRNA and protein levels, while concomitantly increasing mTOR expression. In contrast, inhibition of miR-1825 led to the upregulation of TSC2 and a corresponding decrease in mTOR levels. These outcomes support that TSC2 is a putative target of miR-1825 and further confirm the inverse regulatory relationship between TSC2 and mTOR. Moreover, dysregulation of miR-1825 significantly enhanced cell viability, clonogenic ability, and cell motility in PCa cells. Collectively, these data indicate that miR-1825 promotes tumorigenic phenotypes through the dysregulation of the TSC2/mTOR signaling axis in PCa. In summary, our findings demonstrate that miR-1825 acts as an oncogenic regulator in PCa by targeting TSC2 and modulating the mTOR pathway. The miR-1825/TSC2/mTOR axis may represent a promising therapeutic target for the treatment of PCa.