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

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.