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MiR‐21 upregulation increases IL‐8 expression and tumorigenesis program in airway epithelial cells exposed to cigarette smoke
Author(s) -
Pace Elisabetta,
Di Vincenzo Serena,
Di Salvo Eleonora,
Genovese Sara,
Dino Paola,
Sangiorgi Claudia,
Ferraro Maria,
Gangemi Sebastiano
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28786
Subject(s) - carcinogenesis , a549 cell , stat3 , cancer research , chemistry , downregulation and upregulation , inflammation , tlr4 , stat protein , microrna , gene expression , microbiology and biotechnology , signal transduction , biology , immunology , cell , biochemistry , gene
Background Cigarette smoke exposure, increasing Toll‐like receptor 4 (TLR4) and reactive oxygen species (ROS), promotes inflammatory responses in airway epithelial cells. Chronic inflammation, microRNA (miRNA), and oxidative stress are associated with cancer development. Aims The present study was aimed to explore whether cigarette smoke exposure, altering miR‐21 expression, promoted inflammatory responses and tumorigenesis processes in airway epithelial cells. Methods Airway normal and cancer epithelial cells (16HBE and A549) were exposed to cigarette smoke extracts (CSE) or with/without agomiR‐21, and then it was assessed: a) miR‐21 expression; b) signal transducer and activator of transcription 3 (STAT3) nuclear protein expression and ERK1/2 activation; c) IL‐8 gene expression and protein release. An antagonist of TLR4 (CLI‐095) and the antioxidant flavonoid, apigenin, were also included to evaluate miR‐21 expression in CSE exposed cells. Results It was demonstrated that: a) A549 cells constitutively expressed higher levels of miR‐21 and IL‐8; b) CSE increased STAT3 nuclear expression in 16HBE; c) in both cell lines, CSE and agomiR‐21 increased: miR‐21 expression; ERK1/2 activation and IL‐8 gene expression and protein release; d) TLR4 inhibition counteracted the effects of CSE on miR‐21 in A549; e) apigenin reduced miR‐21 and IL‐8 gene expression in both cell lines. Conclusions Data herein provided identified for the first time new mechanisms supporting the crucial role of cigarette smoke‐induced miR‐21 expression in the amplification of inflammatory responses and in tumorigenesis processes within the airways.