title: microRNA-802/Rnd3 pathway imposes on carcinogenesis and metastasis of fine particulate matter exposure.
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.
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Histology and Embryology, Hebei North University, Zhangjiakou, 075000, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
authors.forename: Na
authors.initials: N
authors.lastname: Gao
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
authors.forename: Runze
authors.initials: R
authors.lastname: Lu
authors.affiliation: Center for Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, 211198, China.
authors.forename: Hongbao
authors.initials: H
authors.lastname: Yang
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
authors.forename: Qingtao
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
authors.forename: Shenshen
authors.initials: S
authors.lastname: Wu
authors.affiliation: School of Public Health, Medical College, Wuhan University of Science and Technology, Wuhan, 430081, China.
authors.forename: Ai-Qun
authors.initials: AQ
authors.lastname: Li
authors.affiliation: Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210009, China.
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.|State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210096, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
mesh_terms: D008841:Actin Cytoskeleton / Q000473:pathology; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D052638:Particulate Matter / Q000633:toxicity*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C552280:MIRN802 microRNA, human; C560526:MIRN802 microRNA, mouse; D035683:MicroRNAs; D052638:Particulate Matter; C513341:Rnd3 protein, mouse; C508705:RND3 protein, human; D020741:rho GTP-Binding Proteins
keywords: PM2.5; actin; carcinogenesis; lung cancer; microRNA