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MiR-21 upregulation increases IL-8 expression and tumorigenesis program in airway epithelial cells exposed to cigarette smoke.

Abstract：

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.

journal_name

J Cell Physiol

journal_title

Journal of cellular physiology

authors

Pace E,Di Vincenzo S,Di Salvo E,Genovese S,Dino P,Sangiorgi C,Ferraro M,Gangemi S

doi

10.1002/jcp.28786

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

22183-22194

issue

12

eissn

0021-9541

issn

1097-4652

journal_volume

234

pub_type

杂志文章

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