NNMT (Nicotinamide N-Methyltransferase)

Our findings further revealed previously uncharacterized somatic copy number alterations, extrachromosomal DNA landscape, and human-HPV fusion peptides, with implications for genetic heterogeneity and therapeutic targets. This study enhances the understanding of cervical cancer through deeper proteogenomic insights, and facilitates the development of personalized therapeutic strategies to improve patient outcomes.

Future research should prioritize the development of potent NNMT inhibitors and further elucidate the role of NNMT in modulating the TME and mediating drug resistance. As a pivotal molecule linking metabolism, epigenetics, and the TME, NNMT offers promising new avenues for BC treatment.

Resistance to NAMPT inhibitors, such as FK866, remains a key limitation to their clinical translation...These findings support the use of NNMT as a predictive biomarker for NAD+-targeting therapies and provide mechanistic insight into a metabolic vulnerability of the CRPC-SCL subtype. Targeting the YAP/NNMT/NAMPT axis may represent a novel strategy for treating stem-like/mesenchymal, therapy-resistant prostate cancers.

Furthermore, our findings demonstrate that the dexamethasone-induced methionine-dependent nicotinamide methylation becomes detrimental for glioblastoma when combined with a methionine-restricted diet. These results show that steroids rewire methionine and nicotinamide metabolism, enabling the development of innovative PET imaging and metabolic therapies for glioblastoma.

It was stated that the AHR, EPHX1, GSTP1, and SLC25A32 did not correlate in healthy intestinal tissue whereas AHCY, ALDH1A1, NNMT, GSTM4, UGT2B17, and SLCO1B3 did not correlate in CRC. The disturbed transcriptional activity of genes related to the biotransformation process at all stages of CRC suggests that this may be the cause of its occurrence; the genes ought to be taken into account in preventive strategies and the treatment of patients.

NNMT is a promising prognostic biomarker and potential therapeutic target in ccRCC, supported by transcriptomic, clinical, and functional validation. While the prognostic relevance of HILPDA remains inconclusive, its metabolic associations suggest potential biological significance. Further studies with larger cohorts and in vivo validation are warranted.

Cells were then subjected to combined treatment with inhibitors and cisplatin (CDDP), and viability and ROS levels were further analyzed. Our results clearly illustrate that cells treated with NNMT inhibitors underwent significant reductions in viability, increased ROS production and activation of apoptotic pathways. Given the association of NNMT with cancer aggressiveness, inhibiting its catalytic activity might present a novel strategy for counteracting cancer growth and chemoresistance, providing the rationale for an effective anti-cancer therapy based on the use of specific NNMT inhibitors.

Concurrently, key oncogenic and metabolic proteins were downregulated, including NNMT (Log2FC = -2.9), PLTP (Log2FC = -2.5), and CYP4X1 (Log2FC = -2.0), which implicated the suppression of MAPK-Akt signaling, ferroptosis activation, and lipid metabolism disruption. These results established a mechanistic rationale for combining postbiotics such as N and UB with standard chemotherapy, highlighting a promising avenue for safer and more effective lymphoma management in the future.

NNMT and NM23A emerge as promising non-invasive biomarkers for RCC, offering substantial diagnostic accuracy and reducing reliance on invasive procedures. Their integration into clinical workflows, supported by advanced machine learning methodologies, could transform RCC diagnostics. Further research with diverse populations is recommended to validate these findings and expand their clinical applicability.