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A miRNA signature for an environmental heterocyclic amine defined by a multi-organ carcinogenicity bioassay in the rat.
Chen, Ying-Shiuan; Wang, Rong; Dashwood, Wan-Mohaiza; Löhr, Christiane V; Williams, David E; Ho, Emily; Mertens-Talcott, Susanne; Dashwood, Roderick H.
Afiliación
  • Chen YS; Center for Epigenetics and Disease Prevention, Texas A&M University College of Medicine, 2121 W Holcombe Blvd., Houston, TX, 77030, USA.
  • Wang R; Linus Pauling Institute, Oregon State University, Corvallis, OR, USA.
  • Dashwood WM; Center for Epigenetics and Disease Prevention, Texas A&M University College of Medicine, 2121 W Holcombe Blvd., Houston, TX, 77030, USA.
  • Löhr CV; College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
  • Williams DE; Linus Pauling Institute, Oregon State University, Corvallis, OR, USA.
  • Ho E; Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, USA.
  • Mertens-Talcott S; Linus Pauling Institute, Oregon State University, Corvallis, OR, USA.
  • Dashwood RH; College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, USA.
Arch Toxicol ; 91(10): 3415-3425, 2017 Oct.
Article en En | MEDLINE | ID: mdl-28289824
Heterocyclic amines (HCAs) produced during high-temperature cooking have been studied extensively in terms of their genotoxic/genetic effects, but recent work has implicated epigenetic mechanisms involving non-coding RNAs. Colon tumors induced in the rat by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) have altered microRNA (miRNA) signatures linked to dysregulated pluripotency factors, such as c-Myc and Krüppel-like factor 4 (KLF4). We tested the hypothesis that dysregulated miRNAs from PhIP-induced colon tumors would provide a "PhIP signature" for use in other target organs obtained from a 1-year carcinogenicity bioassay in the rat. Downstream targets that were corroborated in the rat were then investigated in human cancer datasets. The results confirmed that multiple let-7 family members were downregulated in PhIP-induced skin, colon, lung, small intestine, and Zymbal's gland tumors, and were associated with c-myc and Hmga2 upregulation. PhIP signature miRNAs with the profile mir-21high/mir-126low/mir-29clow/mir-215low/mir-145low were linked to reduced Klf4 levels in rat tumors, and in human pan-cancer and colorectal cancer. It remains to be determined whether this PhIP signature has predictive value, given that more than 20 different genotoxic HCAs are present in the human diet, plus other agents that likely induce or repress many of the same miRNAs. Future studies should define more precisely the miRNA signatures of other HCAs, and their possible value for human risk assessment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pruebas de Carcinogenicidad / Regulación de la Expresión Génica / MicroARNs / Aminas / Neoplasias Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans / Male Idioma: En Revista: Arch Toxicol Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pruebas de Carcinogenicidad / Regulación de la Expresión Génica / MicroARNs / Aminas / Neoplasias Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans / Male Idioma: En Revista: Arch Toxicol Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania