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.

Nicotinamide N-methyltransferase enhances chemoresistance in breast cancer through SIRT1 protein stabilization

“…Hong et al reported that increasing NNMT expression or MNA levels stabilizes SIRT1 protein to regulate hepatic nutrient metabolism [29]. You et al reported NNMT enhances the progression of prostate cancer by stabilizing SIRT1 [30]. These results indicated that NNMT may be a potential therapeutic target not only in cancer but also in other diseases.…”

Hepatoblastomas exhibit markedNNMTdownregulation driven by promoter DNA hypermethylation

“…[35][36][37][38][39] NNMT overexpression has been reported in breast cancer, glioblastoma, and papillary thyroid cancer, among others. 20,40,41 Ulanovskaya et al 42 previously revealed that NNMT overexpression leads to an increase in 1MNA in various aggressive cancer cell lines; the authors proposed that the accumulation of 1MNA caused by NNMT overexpression would sequester methyl groups in cancer cells, leading to diminished methylation with changes in the epigenetic profiles.…”

Elevated N‐methyltransferase expression induced by hepatic stellate cells contributes to the metastasis of hepatocellular carcinoma via regulation of the CD44v3 isoform

“…, TGF‐beta can indeed upregulate the expression of NNMT in hepatoma cells, and the mechanism will continue to be further studied. NNMT methylates NAM and is expressed at high levels in several cancers (Liang et al , ; Pozzi et al , ; Song et al , ; You et al , ) like renal clear cell carcinoma, bladder cancer, and the gastric and colorectal cancers. NNMT KD has similarly been associated with the inhibition of proliferation and/or metastasis of oral squamous carcinoma, renal clear cell carcinoma cells, Panc‐1 pancreatic cancer cells, etc.…”