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

ABSTRACT: Methionine metabolism plays a pivotal role in cancer, with methionine serving as the primary precursor for S-adenosylmethionine (SAM), a critical methyl donor in various methylation processes, including DNA and histone methylation. 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. This resistance is characterized by elevated protein synthesis and reduced apoptosis, suggesting a complex interplay between dietary methionine and NNMT expression in cancer. In summary, this study sheds light on NNMT's multifaceted role in PCa progression, methionine metabolism, and epigenetic regulation. It also highlights potential therapeutic strategies for managing NNMT-negative tumors, offering new avenues for prostate cancer treatment.

ORGANISM(S): Mus musculus

PROVIDER: GSE265811 | GEO | 2026/08/12

REPOSITORIES: GEO