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.
Li, X., Lv, Y., Gao, N., Sun, H., Lu, R., Yang, H., … Chen, R. (2016). microRNA-802/Rnd3 pathway imposes on carcinogenesis and metastasis of fine particulate matter exposure. Oncotarget, 7(23). https://doi.org/10.18632/oncotarget.9019