CircCDR1as mediates PM2.5-induced lung cancer progression by binding to SRSF1.

Research indicates that particulate matter with an aerodynamic equivalent diameter of less than or equal to 2.5 µm in ambient air may induce lung cancer progression. Circular RNAs are a special kind of endogenous noncoding RNA, and their functions are reflected in various diseases and physiological processes, but there are still few studies related to PM 2.5 -induced lung cancer. Here, we identified that circCDR1as was upregulated in lung cancer cells stimulated with PM 2.5 and positively correlated with the malignant features of lung cancer. The lower expression of CircCDR1as reduced the adverse progression of lung cancer cells after PM 2.5 treatment; the lower expression of circCDR1as impaired the growth size and metastatic ability of lung cancer cells in mouse tumour models. Mechanistically, circCDR1as specifically bound to serine/arginine-rich splicing Factor 1 (SRSF1) and affected the splicing of vascular endothelial growth factor-A (VEGFA) by SRSF1. Furthermore, circCDR1as affected SRSF1 function by regulating PARK2-mediated SRSF1 ubiquitination, protein production and degradation. CircCDR1as also affected C-myc and cyclin D1 expression by regulating SRSF1 and affecting the wnt/β-catenin signalling pathway, ultimately promoting malignant behavior and inhibiting the apoptosis of lung cancer cells, thereby causing PM 2.5 -induced lung cancer development. [Display omitted] • CircCDR1as promotes PM 2.5 -induced lung cancer progression. • CircCDR1as binds to SRSF1 protein in PM 2.5 -exposed lung cancer cells. • CircCDR1as and SRSF1 regulate VEGFA mRNA splicing. • CircCDR1as may be a new target for the diagnosis of PM 2.5 -induced lung cancer. [ABSTRACT FROM AUTHOR]