Nicotinamide N-Methyltransferase Remodeled Cell Metabolism and Aggravated Proinflammatory Responses by Activating STAT3/IL1β/PGE₂ Pathway.

ABSTRACT: Nicotinamide N-methyltransferase (NNMT) is a cytosolic methyltransferase, catalyzing N-methylation of nicotinamide (NAM) to form 1-methylnicotinamide (1-MNAM), in which S-adenosyl-l-methionine (SAM) is the methyl donor. It has been well documented that NNMT is elevated in multiple cancers and promotes tumor aggressiveness. In the present study, we investigated the effects of NNMT overexpression on cellular metabolism and proinflammatory responses. We found that NNMT overexpression reduced NAD⁺ and SAM levels, and activated the STAT3 signaling pathway. Consequently, STAT3 activation upregulated interleukin 1β (IL1β) and cyclooxygenase-2 (COX2), leading to prostaglandin E2 (PGE₂) accumulation. On the other hand, NNMT downregulated 15-hydroxyprostaglandin d

SUBMITTER: Yang C 

PROVIDER: S-EPMC9607676 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature