title: Nicotinamide N-methyltransferase enhances the capacity of tumorigenesis associated with the promotion of cell cycle progression in human colorectal cancer cells.
abstract: Nicotinamide N-methyltransferase (NNMT), an enzyme involved in the biotransformation and detoxification of many drugs and xenobiotic compounds, has been found to be overexpressed in several malignancies, including colorectal cancer. However, the biological function of NNMT and the related mechanisms in colorectal cancer have not been elucidated. In the present study, we investigated the effects of NNMT on tumorigenesis by overexpressing NNMT in the human colorectal cancer cells line SW480 which lacks constitutive NNMT expression, and downregulating NNMT expression in HT-29 cells, which exhibit high endogenous expression of NNMT. We found that NNMT significantly accelerates cell proliferation, enhances colony formation in vitro and tumorigenicity in mice; it also inhibits apoptosis, promotes cell cycle progression, increases ATP and 1-methylnicotinamide level and decreases ROS level. We also showed that 1-methylnicotinamide accelerates cell growth, inhibits apoptosis, promotes cell cycle progression, attenuates ROS production and increases ATP level. Our results indicate that NNMT enhances the capacity of tumorigenesis associated with the inhibition of cell apoptosis and the promotion of cell cycle progression in human colorectal cancer cells and the 1-methylnicotinamide increased by NNMT mediates the cellular effects of NNMT in cells. NNMT may play a vital role in energy balance and ROS induction.
authors.affiliation: Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China; Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou 310016, China.
authors.forename: Xinyou
authors.initials: X
authors.lastname: Xie
authors.affiliation: Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China; Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou 310016, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China; Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou 310016, China.
authors.forename: Yanzhong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou 310016, China.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
authors.forename: Guiling
authors.initials: G
authors.lastname: Li
authors.affiliation: Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou 310016, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Ruan
authors.affiliation: Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
authors.forename: Fengying
authors.initials: F
authors.lastname: Li
authors.affiliation: Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou 310016, China.
authors.forename: Huixing
authors.initials: H
authors.lastname: Liu
authors.affiliation: Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China; Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou 310016, China. Electronic address: jameszhang2000@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D050903:Nicotinamide N-Methyltransferase / Q000096:biosynthesis* / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; C494406:NNMT protein, human; D050903:Nicotinamide N-Methyltransferase
keywords: 1-Methylnicotinamide; Apoptosis; Cell cycle; Colorectal cancer; Nicotinamide N-methyltransferase; Tumorigenesis