# Complex roles of nicotinamide N-methyltransferase in cancer progression **Authors:** Weixuan Wang, Changmei Yang, Tianxiang Wang, Haiteng Deng PMC · DOI: 10.1038/s41419-022-04713-z · Cell Death & Disease · 2022-03-25 ## TL;DR This paper reviews how the enzyme NNMT influences cancer development and suggests it could be a useful target for cancer treatment. ## Contribution The paper synthesizes recent findings on NNMT's roles in cancer and highlights its potential as a biomarker and therapeutic target. ## Key findings - NNMT affects NAD+ metabolism and epigenetic states in cancer cells. - High NNMT expression is linked to various cancers and could serve as a biomarker. - NNMT is a potential therapeutic target for cancer treatment. ## Abstract Nicotinamide N-methyltransferase (NNMT) is an intracellular methyltransferase, catalyzing the N-methylation of nicotinamide (NAM) to form 1-methylnicotinamide (1-MNAM), in which S-adenosyl-l-methionine (SAM) is the methyl donor. High expression of NNMT can alter cellular NAM and SAM levels, which in turn, affects nicotinamide adenine dinucleotide (NAD+)-dependent redox reactions and signaling pathways, and remodels cellular epigenetic states. Studies have revealed that NNMT plays critical roles in the occurrence and development of various cancers, and analysis of NNMT expression levels in different cancers from The Cancer Genome Atlas (TCGA) dataset indicated that NNMT might be a potential biomarker and therapeutic target for tumor diagnosis and treatment. This review provides a comprehensive understanding of recent advances on NNMT functions in different tumors and deciphers the complex roles of NNMT in cancer progression. ## Linked entities - **Genes:** NNMT (nicotinamide N-methyltransferase) [NCBI Gene 4837] - **Chemicals:** nicotinamide (PubChem CID 936), 1-methylnicotinamide (PubChem CID 457) ## Full-text entities - **Genes:** Aox1 (aldehyde oxidase 1) [NCBI Gene 11761] {aka Ao, Aox-1, Aox-2, Aox2, Moro, Ro}, Tkfc (triokinase, FMN cyclase) [NCBI Gene 225913] {aka Dak}, AOX1 (aldehyde oxidase 1) [NCBI Gene 316] {aka AO, AOH1}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, VHL (von Hippel-Lindau tumor suppressor) [NCBI Gene 7428] {aka HRCA1, RCA1, VHL1, pVHL}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, PADI2 (peptidyl arginine deiminase 2) [NCBI Gene 11240] {aka PAD-H19, PAD2, PDI2}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, SLC25A1 (solute carrier family 25 member 1) [NCBI Gene 6576] {aka CIC, CMS23, CTP, D2L2AD, SEA, SLC20A3}, PARP1 (poly(ADP-ribose) polymerase 1) [NCBI Gene 142] {aka ADPRT, ADPRT 1, ADPRT1, ARTD1, PARP, PARP-1}, CD38 (CD38 molecule) [NCBI Gene 952] {aka ADPRC 1, ADPRC1, cADPR1}, FHL2 (four and a half LIM domains 2) [NCBI Gene 2274] {aka AAG11, DRAL, FHL-2, SLIM-3, SLIM3}, Padis1 (MMTV LTR integration site 1) [NCBI Gene 111382] {aka Pad-1, Pad1}, Hspa8 (heat shock protein family A (Hsp70) member 8) [NCBI Gene 15481] {aka 2410008N15Rik, Hsc70, Hsc71, Hsc73, Hsp73, Hspa10}, Sirt1 (sirtuin 1) [NCBI Gene 93759] {aka SIR2L1, Sir2, Sir2a, Sir2alpha}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, MAT1A (methionine adenosyltransferase 1A) [NCBI Gene 4143] {aka MAT, MATA1, SAMS, SAMS1}, HPGD (15-hydroxyprostaglandin dehydrogenase) [NCBI Gene 3248] {aka 15-PGDH, PGDH, PGDH1, PHOAR1, SDR36C1}, SDHB (succinate dehydrogenase complex iron sulfur subunit B) [NCBI Gene 6390] {aka CWS2, IP, MC2DN4, PGL4, PPGL4, SDH}, GLI1 (GLI family zinc finger 1) [NCBI Gene 2735] {aka GLI, PAPA8, PPD1}, Ahcy (S-adenosylhomocysteine hydrolase) [NCBI Gene 269378] {aka CuBP, SAHH}, Mat1a (methionine adenosyltransferase 1A) [NCBI Gene 11720] {aka AdoMet, Ams, MAT, MATA1, SAMS, SAMS1}, DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786] {aka ADCADN, AIM, CXXC9, DNMT, HSN1E, MCMT}, NRK (Nik related kinase) [NCBI Gene 203447] {aka NESK}, SHH (sonic hedgehog signaling molecule) [NCBI Gene 6469] {aka HHG1, HLP3, HPE3, MCOPCB5, SMMCI, ShhNC}, SIRT4 (sirtuin 4) [NCBI Gene 23409] {aka SIR2L4}, Nampt (nicotinamide phosphoribosyltransferase) [NCBI Gene 59027] {aka 1110035O14Rik, NAmPRTase, Pbef, Pbef1, Visfatin}, Hpgd (hydroxyprostaglandin dehydrogenase 15 (NAD)) [NCBI Gene 15446] {aka 15-PGDH}, TKFC (triokinase and FMN cyclase) [NCBI Gene 26007] {aka DAK, NET45, TKFCD}, BST1 (bone marrow stromal cell antigen 1) [NCBI Gene 683] {aka CD157, cADPR2}, NNMT (nicotinamide N-methyltransferase) [NCBI Gene 4837], AHCY (adenosylhomocysteinase) [NCBI Gene 191] {aka SAHH, adoHcyase}, FBP1 (fructose-bisphosphatase 1) [NCBI Gene 2203] {aka FBP}, NF1 (neurofibromin 1) [NCBI Gene 4763] {aka NFNS, VRNF, WSS}, AMD1 (adenosylmethionine decarboxylase 1) [NCBI Gene 262] {aka ADOMETDC, AMD, SAMDC}, SIRT7 (sirtuin 7) [NCBI Gene 51547] {aka SIR2L7}, NAPRT (nicotinate phosphoribosyltransferase) [NCBI Gene 93100] {aka NAPRT1, PP3856}, ADA (adenosine deaminase) [NCBI Gene 100] {aka ADA1}, HSPA8 (heat shock protein family A (Hsp70) member 8) [NCBI Gene 3312] {aka HEL-33, HEL-S-72p, HSC54, HSC70, HSC71, HSP71}, Ranbp9 (RAN binding protein 9) [NCBI Gene 56705] {aka IBAP-1, Ibap1, RanBPM}, CYP2E1 (cytochrome P450 family 2 subfamily E member 1) [NCBI Gene 1571] {aka CPE1, CYP2E, P450-J, P450C2E}, NAMPT (nicotinamide phosphoribosyltransferase) [NCBI Gene 10135] {aka 1110035O14Rik, PBEF, PBEF1, VF, VISFATIN}, SP1 (Sp1 transcription factor) [NCBI Gene 6667], PNMT (phenylethanolamine N-methyltransferase) [NCBI Gene 5409] {aka PENT, PNMTase}, Egfr (epidermal growth factor receptor) [NCBI Gene 13649] {aka 9030024J15Rik, Erbb, Errb1, Errp, Wa5, wa-2}, CAVIN1 (caveolae associated protein 1) [NCBI Gene 284119] {aka CAVIN, CGL4, FKSG13, PTRF, cavin-1}, MET (MET proto-oncogene, receptor tyrosine kinase) [NCBI Gene 4233] {aka AUTS9, DA11, DFNB97, HGFR, RCCP2, c-Met}, Bhmt (betaine-homocysteine methyltransferase) [NCBI Gene 12116], Sat1 (spermidine/spermine N1-acetyl transferase 1) [NCBI Gene 20229] {aka SSAT, Sat}, Odc1 (ornithine decarboxylase, structural 1) [NCBI Gene 18263] {aka ODC}, Fbp1 (fructose bisphosphatase 1) [NCBI Gene 14121] {aka Fbp-2, Fbp2, Fbp3}, RET (ret proto-oncogene) [NCBI Gene 5979] {aka CDHF12, CDHR16, HSCR1, MEN2A, MEN2B, MTC1}, Selenbp2 (selenium binding protein 2) [NCBI Gene 20342] {aka AP56, Lpsb2}, QPRT (quinolinate phosphoribosyltransferase) [NCBI Gene 23475] {aka HEL-S-90n, QPRTase}, SAT1 (spermidine/spermine N1-acetyltransferase 1) [NCBI Gene 6303] {aka DC21, KFSD, KFSDX, SAT, SSAT, SSAT-1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Bst1 (bone marrow stromal cell antigen 1) [NCBI Gene 12182] {aka 114/A10, A530073F09, BP-3, Bp3, Bsta1, CD157} - **Diseases:** bladder urothelial carcinoma (MESH:D001749), hypoxia (MESH:D000860), PRAD prostate adenocarcinoma (MESH:D000230), paragangliomas (MESH:D010235), PAAD (MESH:D010190), metastasis (MESH:D009362), UVM uveal melanoma (MESH:C536494), THCA (MESH:D013964), GBM (MESH:D005909), ovarian serous cystadenocarcinoma (MESH:D010049), ACC (MESH:D018268), liver (MESH:D017093), steatohepatitis (MESH:D005234), 1-MANM (MESH:C538557), brain (MESH:D001927), adiposity (MESH:D018205), PCPG (MESH:D010673), glioma (MESH:D005910), uterine corpus endometrial carcinoma (MESH:D016889), CRC (MESH:D015179), kidney and ovarian cancers (MESH:D010051), insulin resistance (MESH:D007333), HGSC (MESH:D008228), CHOL (MESH:D018281), serous carcinoma (MESH:D018297), KIRC (MESH:D002292), uterine carcinosarcoma (MESH:D002296), aggressive (MESH:D010554), HD (MESH:D006816), pancreatic ductal adenocarcinomas (MESH:D021441), pellagra (MESH:D010383), SARC (MESH:D012509), gastric cancer (MESH:D013274), inflammation (MESH:D007249), DLBC (MESH:D016403), OSCC (MESH:D000077195), breast and colon cancer (MESH:D001943), hypoxic (MESH:D002534), LIHC (MESH:D006528), acute myeloid leukemia (MESH:D015470), cervical squamous cell carcinoma (MESH:D002294), TGCT (MESH:C563236), COAD (MESH:D029424), LUAD lung adenocarcinoma (MESH:D000077192), Chromaffin cell tumors (MESH:D005935), glossitis (MESH:D005928), colon adenocarcinoma (MESH:D003110), KICH (MESH:D007674), mitochondrial dysfunction (MESH:D028361), SKCM (MESH:C562393), READ rectum adenocarcinoma (MESH:D012004), cancers (MESH:D009369), stomatitis (MESH:D013280), ESCA esophageal carcinoma (MESH:D004938), NSCLC (MESH:D002289) - **Chemicals:** cholesterol (MESH:D002784), amino acids (MESH:D000596), NAM (MESH:D009536), NAM N-oxide (MESH:C037645), Sinefungin (MESH:C006235), amide (MESH:D000577), GSH (MESH:D005978), TCA (MESH:D014233), quinoline (MESH:C037219), Polyamines (MESH:D011073), noradrenaline (MESH:D009638), folate (MESH:D005492), MgCl2 (MESH:D015636), lysine (MESH:D008239), carnitine (MESH:D002331), Metal (MESH:D008670), Pyrimidine- (MESH:C030986), propylamine (MESH:D011437), lipid (MESH:D008055), dithiothreitol (MESH:D004229), cyclic ADP-ribose (MESH:D036563), 4py (MESH:C016590), spermidine (MESH:D013095), disulfide (MESH:D004220), dopamine (MESH:D004298), adrenaline (MESH:D004837), glutamine (MESH:D005973), EDTA (MESH:D004492), isoquinoline (MESH:C039109), NAD+ (MESH:D009243), glucose (MESH:D005947), tryptophan (MESH:D014364), S-adenosyl-l-homocysteine (MESH:D012435), oxygen (MESH:D010100), catecholamines (MESH:D002395), fatty acid (MESH:D005227), 1-MNAM (MESH:C024058), NA (MESH:D009525), urea (MESH:D014508), ATP (MESH:D000255), lactate (MESH:D019344), PGE2 (MESH:D015232), methionine (MESH:D008715), spermine (MESH:D013096), homocysteine (MESH:D006710), S-adenosyl-L-methionine (MESH:D012436), 2py (-), NADPH (MESH:D009249), triglyceride (MESH:D014280), potassium phosphate (MESH:C013216), pyridines (MESH:D011725), Acetyl-CoA (MESH:D000105), CoA (MESH:D003065), thionicotinamide (MESH:C070820) - **Species:** Mus musculus (house mouse, species) [taxon 10090], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Homo sapiens (human, species) [taxon 9606] - **Cell lines:** CHOL — Homo sapiens (Human), Cholangiocarcinoma, Cancer cell line (CVCL_4Z42), HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), STAD stomach adenocarcinoma — Homo sapiens (Human), Gastric signet ring cell adenocarcinoma, Cancer cell line (CVCL_S859), PANC-1 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_0480), SW480 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0546), HT-29 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0320), SKOV3 — Homo sapiens (Human), Ovarian serous cystadenocarcinoma, Cancer cell line (CVCL_0532), 293 T — Homo sapiens (Human), Transformed cell line (CVCL_0063), MESO mesothelioma — Homo sapiens (Human), Pleural epithelioid mesothelioma, Cancer cell line (CVCL_5113), 769-P — Homo sapiens (Human), Renal cell carcinoma, Cancer cell line (CVCL_1050) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC8956669/full.md ## Figures 6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC8956669/full.md ## References 135 references — full list in the complete paper: https://tomesphere.com/paper/PMC8956669/full.md --- Source: https://tomesphere.com/paper/PMC8956669