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

// Xiaobo Li 1 , Yang lv 2 , Na Gao 1 , Hao Sun 1 , Runze Lu 1 , Hongbao Yang 3 , Chengcheng Zhang 1 , Qingtao Meng 1 , Shenshen Wu 1 , Ai-Qun Li 4 , Yankai Xia 5, * , Rui Chen 1, 6, * 1 Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China 2 Department of Histology and Embryology, Hebei North University, Zhangjiakou, 075000, China 3 Center for Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, 211198, China 4 School of Public Health, Medical College, Wuhan University of Science and Technology, Wuhan, 430081, China 5 Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210009, China 6 State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210096, China * These authors have contributed equally to this work Correspondence to: Rui Chen, e-mail: 101011816@seu.edu.cn Yankai Xia, e-mail: yankaixia@njmu.edu.cn Keywords: PM 2.5 , 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 (PM 2.5 ) to increased lung cancer mortality and morbidity. However, the underlying mechanism causing the adverse effects of PM 2.5 is less clear. In the present study, post-transcriptional profiling was used to explore biological pathways involved in PM 2.5 -induced pulmonary disorders. The carcinogenesis and metastasis of PM 2.5 exposure were evaluated by long-term PM 2.5 exposure tests. We observed dysregulation of actin in A549 cells line and dysplasia in the lungs of mice exposed to PM 2.5 . Both PM 2.5 -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 PM 2.5 promoted carcinogenesis and metastasis of pulmonary cells. Decreased miR-802 expression levels in the serum samples of PM 2.5 -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 PM 2.5 exposure. In addition, long-term exposure to PM 2.5 demonstrated strong associations with malignant pulmonary disorders.