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A Toxicogenomic Approach Reveals a Novel Gene Regulatory Network Active in In Vitro and In Vivo Models of Thyroid Carcinogenesis

Author

Listed:
  • Carla Reale

    (IRGS, Biogem, Via Camporeale, 83031 Ariano Irpino, Avellino, Italy)

  • Filomena Russo

    (IRGS, Biogem, Via Camporeale, 83031 Ariano Irpino, Avellino, Italy)

  • Sara Carmela Credendino

    (Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, 80131 Naples, Italy)

  • Danila Cuomo

    (Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University, College Station, TX 77843, USA
    Department of Science and Technology, University of Sannio, via Port’Arsa 11, 82100 Benevento, Italy)

  • Gabriella De Vita

    (Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, 80131 Naples, Italy)

  • Massimo Mallardo

    (Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, 80131 Naples, Italy)

  • Francesca Pennino

    (Department of Public Health, University of Naples “Federico II”, 80131 Naples, Italy)

  • Immacolata Porreca

    (Human Genetics, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

  • Maria Triassi

    (Department of Public Health, University of Naples “Federico II”, 80131 Naples, Italy)

  • Mario De Felice

    (Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, 80131 Naples, Italy
    IEOS-CNR, Via Pansini 6, 80131 Naples, Italy
    These authors contributed equally to this work and are corresponding authors.)

  • Concetta Ambrosino

    (IRGS, Biogem, Via Camporeale, 83031 Ariano Irpino, Avellino, Italy
    Department of Science and Technology, University of Sannio, via Port’Arsa 11, 82100 Benevento, Italy
    IEOS-CNR, Via Pansini 6, 80131 Naples, Italy
    These authors contributed equally to this work and are corresponding authors.)

Abstract

Epidemiological and experimental studies emphasize the link between environmental chemicals exposure and thyroid cancer. However, this association is strongly debated and the mechanisms of action of environmental thyroid carcinogens still need to be identified. The analysis of in vitro transcriptomic data developed to investigate the effects of chlorpyrifos on immortalized thyrocytes highlighted the impaired expression of genes involved in endodermal carcinogenesis. This endodermal carcinogenic gene-network (ECGN, including Zfp36l2 , Dmbt1 , Ddit4 ), was validated in cellular and mouse models of thyroid carcinogenesis, characterized by the constitutive activation of the mitogen-activated protein kinase (MAPK) pathway and in immortalized thyrocytes exposed to tetrachlorodibenzo- p -dioxin (TCDD) and chlorpyrifos (CPF). The mRNA levels of Zfp36l2 , Dmbt1 and Ddit4 were increased in models characterized by MAPK activation or following TCDD exposure, whereas they were inhibited by CPF exposure. Overall, the ECGN transcripts identify a novel gene-regulatory network associated with thyroid carcinogenesis promoted by genetic mutation or by environmental carcinogens. The latter have opposite effects on the modulation of the ECGN transcripts according to their mechanisms of action in promoting carcinogenesis. Therefore, the analyses of ECGN might be helpful in discriminating compounds that promote cellular survival associated or not to proliferation of thyrocytes.

Suggested Citation

  • Carla Reale & Filomena Russo & Sara Carmela Credendino & Danila Cuomo & Gabriella De Vita & Massimo Mallardo & Francesca Pennino & Immacolata Porreca & Maria Triassi & Mario De Felice & Concetta Ambro, 2019. "A Toxicogenomic Approach Reveals a Novel Gene Regulatory Network Active in In Vitro and In Vivo Models of Thyroid Carcinogenesis," IJERPH, MDPI, vol. 16(1), pages 1-17, January.
    • Handle: RePEc:gam:jijerp:v:16:y:2019:i:1:p:122-:d:194990
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    References listed on IDEAS

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    1. Mitsuhiro Watanabe & Sander M. Houten & Chikage Mataki & Marcelo A. Christoffolete & Brian W. Kim & Hiroyuki Sato & Nadia Messaddeq & John W. Harney & Osamu Ezaki & Tatsuhiko Kodama & Kristina Schoonj, 2006. "Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation," Nature, Nature, vol. 439(7075), pages 484-489, January.
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    Cited by:

    1. SuHyun Lee & YoungWook Lim & YounSeok Kang & KeumJi Jung & SunHa Jee, 2022. "The Association between Blood Concentrations of PCDD/DFs, DL-PCBs and the Risk of Type 2 Diabetes Mellitus and Thyroid Cancer in South Korea," IJERPH, MDPI, vol. 19(14), pages 1-10, July.

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