requirement of riz1 for cancer prevention by methyl-balanced diet要求为癌症预防riz1 methyl-balanced饮食.pdfVIP

Requirement of RIZ1 for Cancer Prevention by Methyl- Balanced Diet 1 1 1 2 1 1 Wenyun Zhou , Sergio Alonso , Daisaku Takai , Shelly C. Lu , Fumiichiro Yamamoto , Manuel Perucho , Shi Huang1,3* 1 Cancer Research Center, The Burnham Institute for Medical Research, La Jolla, California, United States of America, 2 Gastrointestinal and Liver Diseases, USC Research Center for Liver Diseases, USC-UCLA Research Center for Alcoholic Liver and Pancreatic Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America, 3 Institute of Biomedical Sciences, Center for Evolutionary Biology, Fudan University, Shanghai, China Abstract Background: The typical Western diet is not balanced in methyl nutrients that regulate the level of the methyl donor S- adenosylmethionine (SAM) and its derivative metabolite S-adenosylhomocysteine (SAH), which in turn may control the activity of certain methyltransferases. Feeding rodents with amino acid defined and methyl-imbalanced diet decreases hepatic SAM and causes liver cancers. RIZ1 (PRDM2 or KMT8) is a tumor suppressor and functions in transcriptional repression by methylating histone H3 lysine 9. Methodology/Principal Findings: Here we show that a methyl-balanced diet conferred additional survival benefits compared to a tumor-inducing methyl-imbalanced diet only in mice with wild type RIZ1 but not in mice deficient in RIZ1. While absence of RIZ1 was tumorigenic in mice fed the balanced diet, its presence did not prevent tumor formation in mice fed the imbalanced diet. Microarray and gene expression analysis showed that, unlike most of its related enzymes, RIZ1 was upregulated by