NNMT Loss Drives Prostate Cancer Progression through Epigenetic and Metabolic Reprogramming (scRNA-seq)

This study delves into the genetic deletion and silencing of Nicotinamide N-Methyltransferase (NNMT) in prostate cancer (PCa) and its impact on methionine metabolism and cancer progression. We identify significant loss of NNMT expression in PCa and metastatic castration-resistant prostate cancer (CRPC) compared to healthy prostate tissue.

Functional experiments reveal a potential tumor-suppressive role of NNMT in PCa, supported by reduced cell proliferation, colony formation, and sphere formation upon NNMT overexpression. Moreover, we explore the sensitivity of NNMT-positive and NNMT-negative PCa to dietary methionine restriction (MR). NNMT-negative PCa exhibits resistance to MR, which is associated with increased mTORC1 activity.