Importantly, augmentation of NNMT was 5-14-fold greater in human cancerous compared to normal organoids, supporting a role for NNMT in IL-22-mediated colon carcinogenesis.
Additionally, knockdown of NNMT suppressed p-Akt and tumorigenesis, while re-expression of miR-449a induced phosphatase and tensin homolog (PTEN), and inhibited tumor growth.
Our results indicate that NNMT enhances the capacity of tumorigenesis associated with the inhibition of cell apoptosis and the promotion of cell cycle progression in human colorectal cancer cells and the 1-methylnicotinamide increased by NNMT mediates the cellular effects of NNMT in cells.
These results indicate that miR-1291-altered PANC-1 cell function is associated with the increase in N-methylnicotinamide level and NNMT expression, and in turn NNMT may be indicative of the extent of pancreatic carcinogenesis.
Nicotinamide N-methyltransferase (NNMT) is overexpressed in a variety of human cancers, where it contributes to tumorigenesis by a mechanism that is still poorly understood.