{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNicotinamide N‑methyltransferase (NNMT) is an evolutionarily conserved enzyme that catalyzes the transfer of a methyl group from S‑adenosylmethionine (SAM) to nicotinamide, thereby generating 1‑methylnicotinamide and reducing the intracellular pool of methyl donors. This biochemical reaction plays a dual role: it is central to xenobiotic metabolism and it substantially alters the cell’s methylation potential, with downstream consequences on epigenetic regulation such as histone methylation. In diverse settings—from cancer cells to embryonic stem cells—NNMT overexpression drives a reprogramming of the epigenome that is critical for altered gene expression and cell fate determination."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer, aberrant NNMT expression has been implicated in driving multiple oncogenic processes across a wide spectrum of tumor types—including bladder, renal, breast, thyroid, lung, colorectal, pancreatic, melanoma, and others. Elevated NNMT levels contribute to increased cell proliferation, migration, invasion, and therapy resistance. Mechanistically, this is achieved through modulation of key signaling cascades such as PI3K/Akt, SP1/MMP‑2, and the ASK1‑p38 MAPK pathway, while also reprogramming the tumor microenvironment by influencing cancer‐associated fibroblasts and promoting attributes of cancer stem cells. In addition, NNMT has been shown to regulate diagnostic and prognostic markers and may serve as a useful biomarker for assessing disease progression and therapeutic responsiveness."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "38"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nApart from its oncogenic roles, NNMT is critically involved in the regulation of metabolic homeostasis in non‑neoplastic tissues. In hepatic and adipose compartments, NNMT modulates glucose and cholesterol metabolism—effects that are mediated in part by the stabilization of sirtuin proteins—and contributes to the pathophysiology of insulin resistance and metabolic syndrome. NNMT’s functions extend to the central nervous system, where its activity influences neuronal differentiation and cytoprotection, as well as to the vascular endothelium, impacting cell viability under oxidative stress. Moreover, genetic polymorphisms in NNMT have been linked to altered plasma homocysteine levels and increased risk for vascular and developmental disorders such as stroke and congenital heart defects, while its expression in various biofluids underscores its potential as a minimally invasive biomarker."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "39", "end_ref": "48"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Olesya A Ulanovskaya, Andrea M Zuhl, Benjamin F Cravatt "}, {"type": "b", "children": [{"type": "t", "text": "NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Chem Biol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nchembio.1204"}], "href": "https://doi.org/10.1038/nchembio.1204"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23455543"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23455543"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Henrik Sperber, Julie Mathieu, Yuliang Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The metabolome regulates the epigenetic landscape during naive-to-primed human embryonic stem cell transition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb3264"}], "href": "https://doi.org/10.1038/ncb3264"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26571212"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26571212"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yi Peng, Davide Sartini, Valentina Pozzi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis of substrate recognition in human nicotinamide N-methyltransferase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi2007614"}], "href": "https://doi.org/10.1021/bi2007614"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21823666"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21823666"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kamalakannan Palanichamy, Suman Kanji, Nicolaus Gordon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NNMT Silencing Activates Tumor Suppressor PP2A, Inactivates Oncogenic STKs, and Inhibits Tumor Forming Ability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-16-1323"}], "href": "https://doi.org/10.1158/1078-0432.CCR-16-1323"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27810903"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27810903"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Arun Kanakkanthara, Kiran Kurmi, Thomas L Ekstrom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BRCA1 Deficiency Upregulates NNMT, Which Reprograms Metabolism and Sensitizes Ovarian Cancer Cells to Mitochondrial Metabolic Targeting Agents."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-19-1405"}], "href": "https://doi.org/10.1158/0008-5472.CAN-19-1405"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31619387"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31619387"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mark A Eckert, Fabian Coscia, Agnieszka Chryplewicz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41586-019-1173-8"}], "href": "https://doi.org/10.1038/s41586-019-1173-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31043742"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31043742"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Y Wu, M S Siadaty, M E Berens, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overlapping gene expression profiles of cell migration and tumor invasion in human bladder cancer identify metallothionein 1E and nicotinamide N-methyltransferase as novel regulators of cell migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2008.264"}], "href": "https://doi.org/10.1038/onc.2008.264"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18724390"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18724390"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Sai-Wen Tang, Tsung-Cheng Yang, Wei-Chou Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nicotinamide N-methyltransferase induces cellular invasion through activating matrix metalloproteinase-2 expression in clear cell renal cell carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgq225"}], "href": "https://doi.org/10.1093/carcin/bgq225"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21045016"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21045016"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Heba Sh Kassem, Vijay Sangar, Richard Cowan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A potential role of heat shock proteins and nicotinamide N-methyl transferase in predicting response to radiation in bladder cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.10631"}], "href": "https://doi.org/10.1002/ijc.10631"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12216074"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12216074"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yanzhong Wang, Jin Zeng, Weiping Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nicotinamide N-methyltransferase enhances chemoresistance in breast cancer through SIRT1 protein stabilization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast Cancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13058-019-1150-z"}], "href": "https://doi.org/10.1186/s13058-019-1150-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31101119"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31101119"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Mikio Tomida, Iwao Mikami, Shingo Takeuchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serum levels of nicotinamide N-methyltransferase in patients with lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cancer Res Clin Oncol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00432-009-0563-y"}], "href": "https://doi.org/10.1007/s00432-009-0563-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19242722"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19242722"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Jun Zhang, Yanzhong Wang, Guiling Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Down-regulation of nicotinamide N-methyltransferase induces apoptosis in human breast cancer cells via the mitochondria-mediated pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0089202"}], "href": "https://doi.org/10.1371/journal.pone.0089202"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24558488"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24558488"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Jimin Xu, Marco Capezzone, Xiao Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of nicotinamide N-methyltransferase gene promoter by hepatocyte nuclear factor-1beta in human papillary thyroid cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2004-0215"}], "href": "https://doi.org/10.1210/me.2004-0215"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15486044"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15486044"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Xinyou Xie, Huixing Liu, Yanzhong Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nicotinamide N-methyltransferase enhances resistance to 5-fluorouracil in colorectal cancer cells through inhibition of the ASK1-p38 MAPK pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.9962"}], "href": "https://doi.org/10.18632/oncotarget.9962"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27323852"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27323852"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Davide Sartini, Giovanni Muzzonigro, Giulio Milanese, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Upregulation of tissue and urinary nicotinamide N-methyltransferase in bladder cancer: potential for the development of a urine-based diagnostic test."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biochem Biophys (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12013-012-9451-1"}], "href": "https://doi.org/10.1007/s12013-012-9451-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23097023"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23097023"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Xinyou Xie, Haitao Yu, Yanzhong Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nicotinamide N-methyltransferase enhances the capacity of tumorigenesis associated with the promotion of cell cycle progression in human colorectal cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Biochem Biophys (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.abb.2014.08.017"}], "href": "https://doi.org/10.1016/j.abb.2014.08.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25201588"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25201588"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Roberto Campagna, Łukasz Mateuszuk, Kamila Wojnar-Lason, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nicotinamide N-methyltransferase in endothelium protects against oxidant stress-induced endothelial injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2021.119082"}], "href": "https://doi.org/10.1016/j.bbamcr.2021.119082"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34153425"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34153425"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Monica Emanuelli, Andrea Santarelli, Davide Sartini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nicotinamide N-Methyltransferase upregulation correlates with tumour differentiation in oral squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histol Histopathol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.14670/HH-25.15"}], "href": "https://doi.org/10.14670/HH-25.15"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19924637"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19924637"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Tao Yu, Yong-Tao Wang, Pan Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effects of nicotinamide N-methyltransferase on PANC-1 cells proliferation, metastatic potential and survival under metabolic stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000369731"}], "href": "https://doi.org/10.1159/000369731"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25592232"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25592232"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "M G Thomas, M Saldanha, R J Mistry, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nicotinamide N-methyltransferase expression in SH-SY5Y neuroblastoma and N27 mesencephalic neurones induces changes in cell morphology via ephrin-B2 and Akt signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2013.200"}], "href": "https://doi.org/10.1038/cddis.2013.200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23764850"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23764850"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Davide Sartini, Valentina Pozzi, Elisabetta Renzi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of tissue and salivary nicotinamide N-methyltransferase in oral squamous cell carcinoma: basis for the development of a noninvasive diagnostic test for early-stage disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1515/hsz-2012-0112"}], "href": "https://doi.org/10.1515/hsz-2012-0112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22628313"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22628313"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Hui-Chang Bi, Yu-Zhuo Pan, Jing-Xin Qiu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "N-methylnicotinamide and nicotinamide N-methyltransferase are associated with microRNA-1291-altered pancreatic carcinoma cell metabolome and suppressed tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgu174"}], "href": "https://doi.org/10.1093/carcin/bgu174"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25115443"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25115443"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Dong Su Kim, Young Deuk Choi, Mihyang Moon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Composite three-marker assay for early detection of kidney cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Epidemiol Biomarkers Prev (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1055-9965.EPI-12-1156"}], "href": "https://doi.org/10.1158/1055-9965.EPI-12-1156"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23479363"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23479363"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Lise Bathum, Inge Petersen, Lene Christiansen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic and environmental influences on plasma homocysteine: results from a Danish twin study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1373/clinchem.2006.082149"}], "href": "https://doi.org/10.1373/clinchem.2006.082149"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17412799"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17412799"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Agustin Oterino, Maria Toriello, Natalia Valle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The relationship between homocysteine and genes of folate-related enzymes in migraine patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Headache (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1526-4610.2009.01484.x"}], "href": "https://doi.org/10.1111/j.1526-4610.2009.01484.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19619240"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19619240"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Giulia Ganzetti, Davide Sartini, Anna Campanati, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nicotinamide N-methyltransferase: potential involvement in cutaneous malignant melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Melanoma Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/CMR.0000000000000430"}], "href": "https://doi.org/10.1097/CMR.0000000000000430"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29420365"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29420365"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Roberto Campagna, Eleonora Salvolini, Veronica Pompei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nicotinamide N-methyltransferase gene silencing enhances chemosensitivity of melanoma cell lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pigment Cell Melanoma Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/pcmr.12993"}], "href": "https://doi.org/10.1111/pcmr.12993"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34018676"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34018676"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Jie Li, Song You, Sheng Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elevated N-methyltransferase expression induced by hepatic stellate cells contributes to the metastasis of hepatocellular carcinoma via regulation of the CD44v3 isoform."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Oncol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1878-0261.12544"}], "href": "https://doi.org/10.1002/1878-0261.12544"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31294922"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31294922"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Davide Sartini, Riccardo Seta, Valentina Pozzi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of nicotinamide N-methyltransferase in non-small cell lung cancer: in vitro effect of shRNA-mediated gene silencing on tumourigenicity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1515/hsz-2014-0231"}], "href": "https://doi.org/10.1515/hsz-2014-0231"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25204218"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25204218"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Justyna Kanska, Paul-Joseph P Aspuria, Barbie Taylor-Harding, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glucose deprivation elicits phenotypic plasticity via ZEB1-mediated expression of NNMT."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.15429"}], "href": "https://doi.org/10.18632/oncotarget.15429"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28412735"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28412735"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Khin Than Win, Sung-Wei Lee, Hsuan-Ying Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nicotinamide N-methyltransferase overexpression is associated with Akt phosphorylation and indicates worse prognosis in patients with nasopharyngeal carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-013-0980-z"}], "href": "https://doi.org/10.1007/s13277-013-0980-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23838801"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23838801"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Betti Giusti, Claudia Saracini, Paola Bolli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Early-onset ischaemic stroke: analysis of 58 polymorphisms in 17 genes involved in methionine metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1160/TH09-11-0748"}], "href": "https://doi.org/10.1160/TH09-11-0748"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20458436"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20458436"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Mengmeng Song, Ye Li, Mingyong Miao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High stromal nicotinamide N-methyltransferase (NNMT) indicates poor prognosis in colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cam4.2890"}], "href": "https://doi.org/10.1002/cam4.2890"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31989785"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31989785"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Yong Xu, Ping Liu, Dong-Hui Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression profile and prognostic value of NNMT in patients with pancreatic cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.7891"}], "href": "https://doi.org/10.18632/oncotarget.7891"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26942567"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26942567"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Jun Zhang, Xin-you Xie, Su-wen Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nicotinamide N-methyltransferase protein expression in renal cell cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Zhejiang Univ Sci B (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1631/jzus.B0900249"}], "href": "https://doi.org/10.1631/jzus.B0900249"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20104648"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20104648"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Lydi M J W van Driel, Huberdina P M Smedts, Willem A Helbing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Eight-fold increased risk for congenital heart defects in children carrying the nicotinamide N-methyltransferase polymorphism and exposed to medicines and low nicotinamide."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Heart J (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/eurheartj/ehn170"}], "href": "https://doi.org/10.1093/eurheartj/ehn170"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18441319"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18441319"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Valentina Pozzi, Giulia Di Ruscio, Davide Sartini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical performance and utility of a NNMT-based urine test for bladder cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Markers (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.5301/ijbm.5000311"}], "href": "https://doi.org/10.5301/ijbm.5000311"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29148015"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29148015"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Valentina Pozzi, Eleonora Salvolini, Guendalina Lucarini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cancer stem cell enrichment is associated with enhancement of nicotinamide N-methyltransferase expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "IUBMB Life (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/iub.2265"}], "href": "https://doi.org/10.1002/iub.2265"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32150326"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32150326"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Robert de Jonge, Wim J E Tissing, Jan Hendrik Hooijberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms in folate-related genes and risk of pediatric acute lymphoblastic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2008-07-165928"}], "href": "https://doi.org/10.1182/blood-2008-07-165928"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19020309"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19020309"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Aimo Kannt, Anja Pfenninger, Lenore Teichert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of nicotinamide-N-methyltransferase mRNA expression in human adipose tissue and the plasma concentration of its product, 1-methylnicotinamide, with insulin resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetologia (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00125-014-3490-7"}], "href": "https://doi.org/10.1007/s00125-014-3490-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25596852"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25596852"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Juan Carlos Souto, Francisco Blanco-Vaca, José Manuel Soria, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genomewide exploration suggests a new candidate gene at chromosome 11q23 as the major determinant of plasma homocysteine levels: results from the GAIT project."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/430409"}], "href": "https://doi.org/10.1086/430409"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15849667"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15849667"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Jongmin Kim, Seok Joo Hong, Eun Kyung Lim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of nicotinamide N-methyltransferase in hepatocellular carcinoma is associated with poor prognosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1756-9966-28-20"}], "href": "https://doi.org/10.1186/1756-9966-28-20"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19216803"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19216803"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Monika Riederer, Wolfgang Erwa, Robert Zimmermann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adipose tissue as a source of nicotinamide N-methyltransferase and homocysteine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Atherosclerosis (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.atherosclerosis.2008.09.015"}], "href": "https://doi.org/10.1016/j.atherosclerosis.2008.09.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18996527"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18996527"}]}, {"type": "r", "ref": 44, "children": [{"type": "t", "text": "Mikio Tomida, Hideki Ohtake, Takashi Yokota, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stat3 up-regulates expression of nicotinamide N-methyltransferase in human cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cancer Res Clin Oncol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00432-007-0318-6"}], "href": "https://doi.org/10.1007/s00432-007-0318-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17922140"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17922140"}]}, {"type": "r", "ref": 45, "children": [{"type": "t", "text": "B Giusti, C Saracini, P Bolli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic analysis of 56 polymorphisms in 17 genes involved in methionine metabolism in patients with abdominal aortic aneurysm."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2008.057851"}], "href": "https://doi.org/10.1136/jmg.2008.057851"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18635682"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18635682"}]}, {"type": "r", "ref": 46, "children": [{"type": "t", "text": "Lydi M J W van Driel, Marinus J C Eijkemans, Robert de Jonge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Body mass index is an important determinant of methylation biomarkers in women of reproductive ages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Nutr (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3945/jn.109.109710"}], "href": "https://doi.org/10.3945/jn.109.109710"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19812220"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19812220"}]}, {"type": "r", "ref": 47, "children": [{"type": "t", "text": "Karolina Y Liu, Rakhee J Mistry, Carlos A Aguirre, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nicotinamide N-methyltransferase increases complex I activity in SH-SY5Y cells via sirtuin 3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2015.10.023"}], "href": "https://doi.org/10.1016/j.bbrc.2015.10.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26456643"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26456643"}]}, {"type": "r", "ref": 48, "children": [{"type": "t", "text": "Andrzej Fedorowicz, Łukasz Mateuszuk, Grzegorz Kopec, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of the nicotinamide N-methyltransferase (NNMT)-1-methylnicotinamide (MNA) pathway in pulmonary hypertension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Respir Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12931-016-0423-7"}], "href": "https://doi.org/10.1186/s12931-016-0423-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27581040"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27581040"}]}]}]}