Nicotinamide N-methyltransferase enhances the progression of prostate cancer by stabilizing sirtuin 1.

Abstract

A previous study demonstrated that nicotinamide N-methyltransferase (NNMT) is upregulated in the tissues of patients with prostate cancer (PCa); however, the specific underlying mechanism of this remains unclear. To begin with, the expression of NNMT was investigated in the peripheral blood of patients with PCa and of healthy control subjects. The results indicated that the expression level of NNMT was elevated in the peripheral blood and tissues of patients with PCa. Furthermore, the overexpression of NNMT enhanced PC-3 cell viability, invasion and migration capacity. Additionally, the overexpression of NNMT significantly increased the mRNA level of sirtuin 1 (SIRT1) in PC-3 cells. In addition, nicotinamide treatment significantly suppressed the expression of SIRT1 even in PC-3 cells transfected with adeno-associated virus-NNMT. Furthermore, the PC-3 cell invasion capacity was notably decreased by the nicotinamide treatment; however, such effects were largely abolished by the overexpression of NNMT in PC-3 cells. These data indicated that NNMT enhanced PC-3 cell migration and invasion mainly by regulating SIRT1 expression. In summary, the present study indicated that NNMT is an important regulator of SIRT1 expression in PC-3 cells and may be a potential therapeutic target for PCa.