Research Papers:
microRNA-802/Rnd3 pathway imposes on carcinogenesis and metastasis of fine particulate matter exposure
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Abstract
Xiaobo Li1, Yang lv2, Na Gao1, Hao Sun1, Runze Lu1, Hongbao Yang3, Chengcheng Zhang1, Qingtao Meng1, Shenshen Wu1, Ai-Qun Li4, Yankai Xia5,*, Rui Chen1,6,*
1Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China
2Department of Histology and Embryology, Hebei North University, Zhangjiakou, 075000, China
3Center for Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, 211198, China
4School of Public Health, Medical College, Wuhan University of Science and Technology, Wuhan, 430081, China
5Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210009, China
6State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210096, China
*These authors have contributed equally to this work
Correspondence to:
Rui Chen, e-mail: [email protected]
Yankai Xia, e-mail: [email protected]
Keywords: PM2.5, microRNA, lung cancer, carcinogenesis, actin
Received: February 19, 2016 Accepted: April 10, 2016 Published: April 26, 2016
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.
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