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Tobacco-related exposure upregulates circ_0035266 to exacerbate inflammatory responses in human bronchial epithelial cells.

Authors
  • Hua, Qiuhan1, 2
  • Liu, Yufei1, 2
  • Li, Meizhen1, 2
  • Chen, Yingnan2
  • Diao, Qinqin2
  • Zeng, Huixian2
  • Jiang, Yiguo1, 2
  • 1 State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. , (China)
  • 2 Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, China. , (China)
Type
Published Article
Journal
Toxicological Sciences
Publisher
Oxford University Press
Publication Date
Oct 27, 2020
Identifiers
DOI: 10.1093/toxsci/kfaa163
PMID: 33107911
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

One of the most carcinogenic chemicals found in cigarette tobacco smoke is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which has been confirmed to be associated with the etiology of diverse cancers. Lipopolysaccharide (LPS), another biologically active component of cigarette smoke, is a risk factor which enhances NNK-induced lung tumorigenesis due to chronic lung inflammation. While inflammatory responses play critical roles in the initiation of many tumors, our knowledge about the mechanisms of NNK+LPS on inflammation is currently limited. Here, we investigated the inflammatory effects of NNK+LPS in human bronchial epithelial cells (BEAS-2B) and explored the underlying mechanisms mediated by circular RNAs (circRNAs). We identified a novel circRNA, circ_0035266, which was strongly upregulated in NNK+LPS-induced BEAS-2B cells and enhanced the inflammatory responses to NNK+LPS by regulating the secretion of pro-inflammatory cytokines interleukin (IL)-6 and IL-8. Specifically, circ_0035266 knockdown alleviated NNK+LPS-induced inflammatory responses, while overexpression of circ_0035266 had the opposite effect. Moreover, dual luciferase reporter and fluorescence in situ hybridization (FISH) assays verified that circ_0035266 bound to miR-181d-5p directly in the cytoplasm. qRT-PCR, dual luciferase reporter assays and western blot analyses showed that DDX3X (DDX3) was the downstream target of miR-181d-5p and that DDX3X expression levels were modulated by circ_0035266. These results suggested that circ_0035266 served as a competitive endogenous RNA (ceRNA) for miR-181d-5p to regulate DDX3X expression, which is involved in the modulation of NNK+LPS-induced inflammatory responses in BEAS-2B cells. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: [email protected]

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