title: Analysis of the transcriptional regulation of cancer-related genes by aberrant DNA methylation of the cis-regulation sites in the promoter region during hepatocyte carcinogenesis caused by arsenic.
abstract: Liver is the major organ for arsenic methylation metabolism and may be the potential target of arsenic-induced cancer. In this study, normal human liver cell was treated with arsenic trioxide, and detected using DNA methylation microarray. Some oncogenes, tumor suppressor genes, transcription factors (TF), and tumor-associated genes (TAG) that have aberrant DNA methylation have been identified. However, simple functional studies of genes adjacent to aberrant methylation sites cannot well reflect the regulatory relationship between DNA methylation and gene transcription during the pathogenesis of arsenic-induced liver cancer, whereas a further analysis of the cis-regulatory elements and their trans-acting factors adjacent to DNA methylation can more precisely reflect the relationship between them. MYC and MAX (MYC associated factor X) were found to participating cell cycle through a bioinformatics analysis. Additionally, it was found that the hypomethylation of cis-regulatory sites in the MYC promoter region and the hypermethylation of cis-regulatory sites in the MAX promoter region result in the up-regulation of MYC mRNA expression and the down-regulation of MAX mRNA, which increased the hepatocyte carcinogenesis tendency.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Miao
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
authors.forename: Xianzhi
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.affiliation: Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Qiao
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
authors.forename: Weihui
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
authors.forename: Dongbo
authors.initials: D
authors.lastname: Xue
mesh_terms: D020816:Amino Acid Motifs; D000077237:Arsenic Trioxide; D001152:Arsenicals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D063646:Carcinogenesis; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019295:Computational Biology; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D008099:Liver / Q000187:drug effects; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010087:Oxides / Q000633:toxicity; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D001152:Arsenicals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C499330:MAX protein, human; D010087:Oxides; D012333:RNA, Messenger; D014157:Transcription Factors; D051153:Wnt Proteins; D000077237:Arsenic Trioxide
keywords: DNA methylation; arsenic exposure; carcinogenesis