title: N-methylnicotinamide and nicotinamide N-methyltransferase are associated with microRNA-1291-altered pancreatic carcinoma cell metabolome and suppressed tumorigenesis.
abstract: The cell metabolome comprises abundant information that may be predictive of cell functions in response to epigenetic or genetic changes at different stages of cell proliferation and metastasis. An unbiased ultra-performance liquid chromatography-mass spectrometry-based metabolomics study revealed a significantly altered metabolome for human pancreatic carcinoma PANC-1 cells with gain-of-function non-coding microRNA-1291 (miR-1291), which led to a lower migration and invasion capacity as well as suppressed tumorigenesis in a xenograft tumor mouse model. A number of metabolites, including N-methylnicotinamide, involved in nicotinamide metabolism, and l-carnitine, isobutyryl-carnitine and isovaleryl-carnitine, involved in fatty acid metabolism, were elevated in miR-1291-expressing PANC-1. Notably, N-methylnicotinamide was elevated to the greatest extent, and this was associated with a sharp increase in nicotinamide N-methyltransferase (NNMT) mRNA level in miR-1291-expressing PANC-1 cells. In addition, expression of NNMT mRNA was inversely correlated with pancreatic tumor size in the xenograft mouse model. These results indicate that miR-1291-altered PANC-1 cell function is associated with the increase in N-methylnicotinamide level and NNMT expression, and in turn NNMT may be indicative of the extent of pancreatic carcinogenesis.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China, Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Hui-Chang
authors.initials: HC
authors.lastname: Bi
authors.affiliation: Department of Pharmaceutical Sciences, SUNY-Buffalo, Buffalo, NY 14214, USA, Department of Biochemistry & Molecular Medicine, UC Davis Medical Center, Sacramento, CA 95817, USA and.
authors.forename: Yu-Zhuo
authors.initials: YZ
authors.lastname: Pan
authors.affiliation: Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: Jing-Xin
authors.initials: JX
authors.lastname: Qiu
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Kristopher W
authors.initials: KW
authors.lastname: Krausz
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Caroline H
authors.initials: CH
authors.lastname: Johnson
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Chang-Tao
authors.initials: CT
authors.lastname: Jiang
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
authors.affiliation: Department of Pharmaceutical Sciences, SUNY-Buffalo, Buffalo, NY 14214, USA, Department of Biochemistry & Molecular Medicine, UC Davis Medical Center, Sacramento, CA 95817, USA and aimyu@ucdavis.edu.
authors.forename: Ai-Ming
authors.initials: AM
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D055442:Metabolome; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000378:metabolism; D050903:Nicotinamide N-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C587958:MIRN1291 microRNA, human; D035683:MicroRNAs; D009536:Niacinamide; C494406:NNMT protein, human; D050903:Nicotinamide N-Methyltransferase; C008472:N-methylnicotinamide