title: Genome-wide analysis of DNA methylation in UVB- and DMBA/TPA-induced mouse skin cancer models.
abstract: OBJECTIVE
  Ultraviolet irradiation and carcinogens have been reported to induce epigenetic alterations, which potentially contribute to the development of skin cancer. We aimed to study the genome-wide DNA methylation profiles of skin cancers induced by ultraviolet B (UVB) irradiation and 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-1,3-acetate (TPA).
  
  
  METHODS
  Methylated DNA immunoprecipitation (MeDIP) followed by next-generation sequencing was utilized to ascertain the DNA methylation profiles in the following common mouse skin cancer models: SKH-1 mice treated with UVB irradiation and CD-1 mice treated with DMBA/TPA. Ingenuity® Pathway Analysis (IPA) software was utilized to analyze the data and to identify gene interactions among the different pathways.
  
  
  RESULTS
  6003 genes in the UVB group and 5424 genes in the DMBA/TPA group exhibited a greater than 2-fold change in CpG methylation as mapped by the IPA software. The top canonical pathways identified by IPA after the two treatments were ranked were pathways related to cancer development, cAMP-mediated signaling, G protein-coupled receptor signaling and PTEN signaling associated with UVB treatment, whereas protein kinase A signaling and xenobiotic metabolism signaling were associated with DMBA/TPA treatment. In addition, the mapped IL-6-related inflammatory pathways displayed alterations in the methylation profiles of inflammation-related genes linked to UVB treatment.
  
  
  CONCLUSIONS
  Genes with altered methylation were ranked in the UVB and DMBA/TPA models, and the molecular interaction networks of those genes were identified by the IPA software. The genome-wide DNA methylation profiles of skin cancers induced by UV irradiation or by DMBA/TPA will be useful for future studies on epigenetic gene regulation in skin carcinogenesis.
authors.affiliation: Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA; Department of Pharmaceutics, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA; Graduate Program in Pharmaceutical Sciences, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA.
authors.forename: Anne Yuqing
authors.initials: AY
authors.lastname: Yang
authors.affiliation: Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA; Department of Pharmaceutics, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA; Department of Food Science and Biotechnology, CHA university, Kyunggi, Korea.
authors.forename: Jong Hun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA; Department of Pharmaceutics, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA.
authors.forename: Limin
authors.initials: L
authors.lastname: Shu
authors.affiliation: Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA; Department of Pharmaceutics, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA; Graduate Program in Pharmaceutical Sciences, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA.
authors.forename: Chengyue
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA; Department of Pharmaceutics, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA.
authors.forename: Zheng-Yuan
authors.initials: ZY
authors.lastname: Su
authors.affiliation: Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA; Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA.
authors.forename: Yaoping
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA; Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA.
authors.forename: Mou-Tuan
authors.initials: MT
authors.lastname: Huang
authors.affiliation: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA; Graduate Program in Cellular and Molecular Pharmacology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Ramirez
authors.affiliation: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Pung
authors.affiliation: Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA; Department of Pharmaceutics, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA; Graduate Program in Pharmaceutical Sciences, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Verzi
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Hart
authors.affiliation: Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA; Department of Pharmaceutics, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA; Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA. Electronic address: kongt@pharmacy.rutgers.edu.
authors.forename: Ah-Ng Tony
authors.initials: AN
authors.lastname: Kong
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000737:chemistry; D000818:Animals; D002273:Carcinogens / Q000737:chemistry; D018899:CpG Islands; D019175:DNA Methylation; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D007249:Inflammation; D051379:Mice; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000737:chemistry; D014466:Ultraviolet Rays
chemical_list: C554292:12-O-tetradecanoylphorbol-1,3-acetate; D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate
keywords: DMBA/TPA; DNA methylation; Epigenetics; MeDIP-Seq; UVB
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