Affiliation:
1. State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, P.R. China
2. Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 511436, P.R. China
Abstract
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. Although 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, whereas 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 for miR-181d-5p to regulate DDX3X expression, which is involved in the modulation of NNK+LPS-induced inflammatory responses in BEAS-2B cells.
Funder
National Natural Science Foundation of China
Science and Technology Program of Guangzhou
Guangdong Natural Science Foundation
University Chief Scientist Program of Guangzhou
Medical Scientific Research Foundation of Guangdong Province of China
Publisher
Oxford University Press (OUP)
Cited by
9 articles.
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