Cancer is the main leading cause of death in the world, although it has been made noteworthy advances in cancer research in the past decades. Early detection of cancer is extremely important in improving the chances of successful therapy. Thus, it is urgently needed to make further efforts to explore novel tumor markers for treatment. Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme which catalyzes the N-methylation of nicotinamide to form 1-methylnicotinamide (1-MNA), and plays an important role in controlling the intracellular concentration of nicotinamide. Nicotinamide, the precursor to NAD+, is an important cofactor that associates cellular redox states with energy metabolism. Growing evidence shows that NNMT protein levels are elevated in a variety of human cancers, and increased NNMT expression has been linked to tumor aggressiveness. This paper presents a review for the role of NNMT expressed in a series of human cancers and the regulating mechanism involved, and offers its potential value of NNMT in cancer detection and treatment.
Dihydrolipoamide S-acetyltrans-ferase (DLAT), a mitochondrial protein involved in glucose metabolism, has been identified as a key gene associated with cuproptosis recently. However, studies on DLAT in pan-cancer have not been found. Aim of this study is to explore the expression profiles and clinical value of DLAT in pan-cancer. DLAT expression profiles were obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), UALCAN and the Human Protein Atlas (HPA) websites. The prognostic and diagnostic values of DLAT and its relationship with immune cell infiltration were analyzed based on TCGA data. cBioPortal and UALCAN websites were used to search gene alteration and methylation status of DLAT in tumors, respectively. CancerSEA database was used to investigate the biological functions of DLAT at the single-cell level. Finally, STRING, GAPIA2.0 and TIMER databases were used to construct protein-protein interaction (PPI) networks and functional enrichment analyses. High DLAT expression was found in most cancers and predicted poor prognosis in patients with several tumors, such as breast cancer, esophageal cancer, head and neck squamous cell carcinoma. DLAT showed early diagnostic value in 17 tumors, especially in acute myeloid leukemia (LAML). Abnormal gene alterations and DNA methylation of DLAT were verified in pan-cancer. Single cell RNA sequencing (scRNAseq) analysis reflected that DLAT could regulate various biological functions of cancer cells. Abnormal expression of DLAT regulated infiltration of multiple immune cells in a variety of tumors. Gene enrichment analysis showed that DLAT was involved in mitochondrial matrix, coated vesicle and ribonucleoprotein granule. DLAT can be used as an important indicator of early diagnosis, prognosis and immunotherapy for a variety of tumors.
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