PMID- 33107911
OWN - NLM
STAT- MEDLINE
DCOM- 20210818
LR  - 20231213
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 179
IP  - 1
DP  - 2021 Jan 6
TI  - Tobacco-Related Exposure Upregulates Circ_0035266 to Exacerbate Inflammatory 
      Responses in Human Bronchial Epithelial Cells.
PG  - 70-83
LID - 10.1093/toxsci/kfaa163 [doi]
AB  - 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.
CI  - (c) The Author(s) 2020. Published by Oxford University Press on behalf of the 
      Society of Toxicology. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Hua, Qiuhan
AU  - Hua Q
AD  - State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of 
      Guangzhou Medical University, Guangzhou 510120, P.R. China.
AD  - Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 
      511436, P.R. China.
FAU - Liu, Yufei
AU  - Liu Y
AD  - State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of 
      Guangzhou Medical University, Guangzhou 510120, P.R. China.
AD  - Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 
      511436, P.R. China.
FAU - Li, Meizhen
AU  - Li M
AD  - State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of 
      Guangzhou Medical University, Guangzhou 510120, P.R. China.
AD  - Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 
      511436, P.R. China.
FAU - Chen, Yingnan
AU  - Chen Y
AD  - Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 
      511436, P.R. China.
FAU - Diao, Qinqin
AU  - Diao Q
AD  - Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 
      511436, P.R. China.
FAU - Zeng, Huixian
AU  - Zeng H
AD  - Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 
      511436, P.R. China.
FAU - Jiang, Yiguo
AU  - Jiang Y
AD  - State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of 
      Guangzhou Medical University, Guangzhou 510120, P.R. China.
AD  - Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 
      511436, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (MicroRNAs)
RN  - 0 (Tobacco Smoke Pollution)
SB  - IM
MH  - Apoptosis
MH  - Cell Proliferation
MH  - Epithelial Cells
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *MicroRNAs/genetics
MH  - Nicotiana/toxicity
MH  - *Tobacco Smoke Pollution
OTO - NOTNLM
OT  - DDX3X
OT  - NNK
OT  - circ_0035266
OT  - inflammation
OT  - miR-181d-5p
EDAT- 2020/10/28 06:00
MHDA- 2021/08/19 06:00
CRDT- 2020/10/27 12:14
PHST- 2020/10/28 06:00 [pubmed]
PHST- 2021/08/19 06:00 [medline]
PHST- 2020/10/27 12:14 [entrez]
AID - 5941476 [pii]
AID - 10.1093/toxsci/kfaa163 [doi]
PST - ppublish
SO  - Toxicol Sci. 2021 Jan 6;179(1):70-83. doi: 10.1093/toxsci/kfaa163.