The effects for PM2.5 exposure on non-small-cell lung cancer induced motility and proliferation

Background: Increasing urbanization and associated air pollution, including elevated levels of particulate matter (PM), are strongly correlated with the development of various respiratory diseases. In particular, PM2.5 has been implicated in promoting lung cancer initiation, growth and progression. Cell migration and proliferation are crucial for the progression of cancer. However, the molecular signatures and biological networks representing the distinct and shared features of non-small cell lung cancer (NSCLC) after PM2.5 exposure are unknown. Results: Functional assays demonstrated higher proliferation, migration and invasion of cancer cells stimulated with PM2.5. To investigate the complicated mechanisms, we performed global transcriptome profiling of the A549 cell line. Particularly, transcriptome sequencing revealed invasive characteristics reminiscent of cancer cells. By comparing the transcriptomes, we identified distinct molecular signatures and cellular processes defining the invasive and proliferative properties of PM2.5-exposed cells, respectively. Interestingly, under the PM2.5-stimulated condition, the A549 and H1299 cells strengthened obviously properties in motility and proliferation. Based on the network model reconstructing the shared protein-protein interactions, we selected the two most up-regulated genes, interleukin-1 beta (IL1 beta) and matrix metalloprotease 1 (MMP1), as key regulators responsible for the effects of PM2.5 exposure. Notably, IL1 beta and MMP1 expression was elevated in independent assays, which was further enhanced by PM2.5. Conclusion: Taken together, our systems approach to investigating PM2.5 exposure provides a basis to identify key regulators responsible for the pathological features of NSCLC.