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The Potential Key Role of the NRF2/NQO1 Pathway in the Health Effects of Arsenic Pollution on SCC

Author

Listed:
  • Qianlei Yang

    (Department of Toxicology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou 215123, China
    These authors contributed equally to this work.)

  • Rui Yan

    (Department of Toxicology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou 215123, China
    These authors contributed equally to this work.)

  • Yuemei Mo

    (Physical Examination Department, Center for Disease Control and Prevention of Suzhou Industrial Park, Suzhou 215100, China
    These authors contributed equally to this work.)

  • Haixuan Xia

    (Department of Toxicology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou 215123, China)

  • Hanyi Deng

    (Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China)

  • Xiaojuan Wang

    (Department of Toxicology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou 215123, China)

  • Chunchun Li

    (Changzhou Wujin District Center for Disease Control and Prevention, Changzhou 213164, China)

  • Koichi Kato

    (Laboratory of Environmental Toxicology and Carcinogenesis, School of Pharmacy, Nihon University, Chiba 274-8555, Japan)

  • Hengdong Zhang

    (Department of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210028, China
    Jiangsu Preventive Medicine Association, Nanjing 210009, China)

  • Tingxu Jin

    (Department of Toxicology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou 215123, China
    School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 550025, China)

  • Jie Zhang

    (Department of Toxicology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou 215123, China)

  • Yan An

    (Department of Toxicology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou 215123, China)

Abstract

Arsenic is widely present in nature and is a common environmental poison that seriously damages human health. Chronic exposure to arsenic is a major environmental poisoning factor that promotes cell proliferation and leads to malignant transformation. However, its molecular mechanism remains unclear. In this study, we found that arsenite can promote the transformation of immortalized human keratinocyte cells (HaCaT) from the G0/G1 phase to S phase and demonstrated malignant phenotypes. This phenomenon is accompanied by obviously elevated levels of NRF2, NQO1, Cyclin E, and Cyclin-dependent kinase 2 (CDK2). Silencing the NRF2 expression with small interfering RNA (siRNA) in arsenite-transformed (T-HaCaT) cells was shown to reverse the malignant phenotype. Furthermore, the siRNA silencing of NQO1 significantly decreased the levels of the cyclin E-CDK2 complex, inhibiting the G0/G1 to S phase cell cycle progression and transformation to the T-HaCaT phenotypes. Thus, we hypothesized that the NRF2/NQO1 pathway played a key role in the arsenite-induced malignancy of HaCaT cells. By increasing the expression of Cyclin E-CDK2, the NRF2/NQO1 pathway can affect cell cycle progression and cell proliferation. A new common health effect mechanism of arsenic carcinogenesis has been identified; thus, it would contribute to the development of novel treatments to prevent and treat skin cancer caused by arsenic.

Suggested Citation

  • Qianlei Yang & Rui Yan & Yuemei Mo & Haixuan Xia & Hanyi Deng & Xiaojuan Wang & Chunchun Li & Koichi Kato & Hengdong Zhang & Tingxu Jin & Jie Zhang & Yan An, 2022. "The Potential Key Role of the NRF2/NQO1 Pathway in the Health Effects of Arsenic Pollution on SCC," IJERPH, MDPI, vol. 19(13), pages 1-16, July.
    • Handle: RePEc:gam:jijerp:v:19:y:2022:i:13:p:8118-:d:854101
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    References listed on IDEAS

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    1. Thomas M. Missimer & Christopher M. Teaf & William T. Beeson & Robert G. Maliva & John Woolschlager & Douglas J. Covert, 2018. "Natural Background and Anthropogenic Arsenic Enrichment in Florida Soils, Surface Water, and Groundwater: A Review with a Discussion on Public Health Risk," IJERPH, MDPI, vol. 15(10), pages 1-30, October.
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