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.

Function of PM2.5 in the pathogenesis of lung cancer and chronic airway inflammatory diseases (Review)

“…Another study investigated the association between PM2.5 exposure and the miR-802/Rho family GTPase 3 (Rnd3) pathway in lung cancer in vivo and in vitro. PM2.5 was demonstrated to enhance the growth and metastasis of lung cancer (38). These results warrant further investigation of PM2.5-induced miR changes in lung cancer.…”

DR4 mediates the progression, invasion, metastasis and survival of colorectal cancer through the Sp1/NF1 switch axis on genomic locus

“…22 Briefly, lentiviral particles were mixed gently, and added to colorectal cancer cells. 22 Briefly, lentiviral particles were mixed gently, and added to colorectal cancer cells.…”

“…22 In brief, for colony formation assays, 500 colorectal cancer cells were seeded in 10 cm plates and allowed to grow in complete medium for 10 days. 22 In brief, for colony formation assays, 500 colorectal cancer cells were seeded in 10 cm plates and allowed to grow in complete medium for 10 days.…”

“…Lentiviral expression plasmid that harbored a firefly luciferase cDNA and lentiviruses were generated as described previously. 22 Briefly, lentiviral particles were mixed gently, and added to colorectal cancer cells. After transduction with lentivirus for 12 hr, we replaced the culture medium with complete medium containing 7.5 lg ml 21 blasticidin S (InvivoGen, San Diego, CA, USA), and replaced it every 2 days for the next 1 week after all control cells died.…”

“…The detailed procedure for these assays has previously been described. 22 In brief, for colony formation assays, 500 colorectal cancer cells were seeded in 10 cm plates and allowed to grow in complete medium for 10 days. For the cell invasion assays, 1 3 10 5 cells were plated into the Transwell insert coated with Matrigel (CytoSelect 24-Well Cell Invasion Assay Kit; Cell Biolabs, USA), and cultured with complete medium for 48 hr.…”