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Circ0087385 promotes DNA damage in benzo(a)pyrene-induced lung cancer development by upregulating CYP1A1.
Zhang, Nan; Qiu, Miaoyun; Yao, Shuwei; Zhou, Hanyu; Zhang, Han; Jia, Yangyang; Li, Xin; Chen, Xintong; Li, Xun; Zhou, Yun; Jiang, Yiguo.
Afiliación
  • Zhang N; The Key Laboratory of Advanced Interdisciplinary Studies, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 511436, China.
  • Qiu M; Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 511436, China.
  • Yao S; The Key Laboratory of Advanced Interdisciplinary Studies, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 511436, China.
  • Zhou H; Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 511436, China.
  • Zhang H; Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 511436, China.
  • Jia Y; Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 511436, China.
  • Li X; Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 511436, China.
  • Chen X; Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 511436, China.
  • Li X; Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 511436, China.
  • Zhou Y; Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 511436, China.
  • Jiang Y; Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 511436, China.
Toxicol Sci ; 198(2): 221-232, 2024 Mar 26.
Article en En | MEDLINE | ID: mdl-38310363
ABSTRACT
Increasing environmental genotoxic chemicals have been shown to induce epigenetic alterations. However, the interaction between genetics and epigenetics in chemical carcinogenesis is still not fully understood. Here, we constructed an in vitro human lung carcinogenesis model (16HBE-T) by treating human bronchial epithelial cells with a typical significant carcinogen benzo(a)pyrene (BaP). We identified a novel circular RNA, circ0087385, which was overexpressed in 16HBE-T and human lung cancer cell lines, as well as in lung cancer tissues and serum exosomes from lung cancer patients. The upregulated circ0087385 after exposure to BaP promoted DNA damage in the early stage of chemical carcinogenesis and affected the cell cycle, proliferation, and apoptosis of the malignantly transformed cells. Overexpression of circ0087385 enhanced the expression of cytochrome P450 1A1 (CYP1A1), which is crucial for metabolically activating BaP. Interfering with circ0087385 or CYP1A1 reduced the levels of ultimate carcinogen benzo(a)pyrene diol epoxide (BPDE) and BPDE-DNA adducts. Interfering with CYP1A1 partially reversed the DNA damage induced by high expression of circ0087385, as well as decreased the level of BPDE and BPDE-DNA adducts. These findings provide novel insights into the interaction between epigenetics and genetics in chemical carcinogenesis which are crucial for understanding the epigenetic and genetic toxicity of chemicals.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Citocromo P-450 CYP1A1 / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Toxicol Sci Asunto de la revista: TOXICOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Citocromo P-450 CYP1A1 / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Toxicol Sci Asunto de la revista: TOXICOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos