期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 282, 期 1, 页码 9-19出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2014.10.022
关键词
IncRNAs; Inflammation; Epithelial-mesenchymal transition (EMT); Cancer stem cells (CSCs); Cigarette smoke extract (CSE); Carcinogenesis
资金
- Natural Science Foundations of China [81273114]
- Key Program of Educational Commission of Jiangsu Province of China [11KJA330002]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
The incidence of lung diseases, including cancer, caused by cigarette smoke is increasing, but the molecular mechanisms of gene regulation induced by cigarette smoke remain unclear. This report describes a long noncoding RNA (IncRNA) that is induced by cigarette smoke extract (CSE) and experiments utilizing IncRNAs to integrate inflammation with the epithelial-mesenchymal transition (EMT) in human bronchial epithelial (HBE) cells. The present study shows that, induced by CSE, IL-6, a pro-inflammatory cytokine, leads to activation of STAT3, a transcription activator. A ChIP assay determined that the interaction of STAT3 with the promoter regions of HOX transcript antisense RNA (HOTAIR) increased levels of HOTAIR. Blocking of IL-6 with anti-IL-6 antibody, decreasing STAT3, and inhibiting STAT3 activation reduced HOTAIR expression. Moreover, for HBE cells cultured in the presence of HOTAIR siRNA for 24 h, the CSE-induced EMT, formation of cancer stem cells (CSCs), and malignant transformation were reversed. Thus, IL-6, acting on STAT3 signaling, which up-regulates HOTAIR in an autocrine manner, contributes to the EMT and to CSCs induced by CSE. These data define a link between inflammation and EMT, processes involved in the malignant transformation of cells caused by CSE. This link, mediated through IncRNAs, establishes a mechanism for CSE-induced lung carcinogenesis. (C) 2014 Elsevier Inc. All rights reserved.
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