RNA and PTBP1-RIP sequencing in BEAS-2B cells with circFCHO2 overexpression and knockdown

Circular RNAs (circRNAs) have emerged as key regulators in human diseases, yet their mechanisms of action in chronic obstructive pulmonary disease (COPD) remain largely unknown. We report a mammalian conserved circRNA circFCHO2 is identified to play critical roles in COPD. The expression level of circFCHO2 was significantly increased in COPD cell models, mouse models, and human lung tissue samples. Meanwhile, we demonstrated that circFCHO2 promotes epithelial-to-mesenchymal transition (EMT) of bronchial epithelial cells and extracellular matrix (ECM) remodeling. Mechanistically, circFCHO2 binds to and facilitates the nuclear translocation of PTBP1, thereby inhibiting the splicing of GRN pre-mRNA, which reduces PGRN protein expression levels. This activation of the NF-κB signaling pathway regulates the expression of EMT and ECM remodeling-related proteins, leading to the occurrence of airway remodeling. Overall, our study advanced the understanding of the molecular mechanisms by which circRNAs contribute to the airway remodeling of COPD.