MicroRNA-802/Rnd3 pathway imposes on carcinogenesis and metastasis of fine particulate matter exposure

Xiaobo Li,Hao Sun,Hongbao Yang,Yankai Xia,Ai-Qun Li,Chengcheng Zhang,Qingtao Meng,Runze Lu,Shenshen Wu,Na Gao,Yang Lv,Rui Chen

doi:10.18632/oncotarget.9019

Abstract

Recent studies have linked ambient fine particulate matter (PM2.5) to increased lung cancer mortality and morbidity. However, the underlying mechanism causing the adverse effects of PM2.5 is less clear. In the present study, post-transcriptional profiling was used to explore biological pathways involved in PM2.5-induced pulmonary disorders. The carcinogenesis and metastasis of PM2.5 exposure were evaluated by long-term PM2.5 exposure tests. We observed dysregulation of actin in A549 cells line and dysplasia in the lungs of mice exposed to PM2.5. Both PM2.5-exposed cells and animals showed increased Rnd3 expression levels. Moreover, miR-802 mimics rescued actin disorganization in vitro and alveolitis in vivo. Long-term exposure to PM2.5 promoted carcinogenesis and metastasis of pulmonary cells. Decreased miR-802 expression levels in the serum samples of PM2.5-treated mice and individuals from moderately polluted cities were observed. Increased Rnd3 expression levels in lung cancers tissues have been identified by a genome database TCGA, and have been linked to less overall survival probabilities of lung cancer patients. Our findings suggest that dysregulation of actin cytoskeleton and down-regulation of miR-802 expression might be the underlying mechanism involved in the adverse effects of PM2.5 exposure. In addition, long-term exposure to PM2.5 demonstrated strong associations with malignant pulmonary disorders.

Highlights

Previous studies have highlighted the relationship of PM2.5 exposure to the exacerbation of asthma, bronchitis, chronic obstructive pulmonary disease (COPD), and lung cancer [1,2,3,4]
Our findings suggest that dysregulation of actin cytoskeleton and down-regulation of miR-802 expression might be the underlying mechanism involved in the adverse effects of PM2.5 exposure
A total of 20 modulated miRNAs from 500 μg/ mL PM2.5-treated A549 cells (Table 1) were identified according to cut-off, as fold change > 2 and false discovery rate (FDR) < 0.05, and the potential target mRNAs of miRNAs were predicted by miRWalk

Summary

Introduction

Previous studies have highlighted the relationship of PM2.5 exposure to the exacerbation of asthma, bronchitis, chronic obstructive pulmonary disease (COPD), and lung cancer [1,2,3,4]. Population based studies strengthen the evidence that PM2.5 are correlated to increases in lung cancer mortality [5,6,7]. Several www.impactjournals.com/oncotarget studies have investigated changes in miRNAs expression in response to PM2.5 or its major components. Jardim et al [11] first reported that diesel exhaust particles induced dysregulation of miRNAs expression in human airway cells, which may be related to tumorigenesis. PM, carbon black particles, and metal-rich particles reportedly induced altered miRNAs exposure in vitro, in animal models and human leukocytes [12,13,14,15]

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Results

Conclusion