circFOXP1 Promotes Pancreatic Ductal Adenocarcinoma Progression Through Regulating EREG/MAPK/ERK Axis.

Circular RNAs (circRNAs) are indispensable for triggering pancreatic ductal adenocarcinoma (PDAC) progression. However, the specific biological processes and mechanisms by which circRNAs influence PDAC remain largely unknown. Here, we reported that circFOXP1 is a critical promoter of PDAC progression, exhibiting marked upregulation in patient tumour tissues that correlates with advanced TNM stage and poor prognosis. Functional studies demonstrate that circFOXP1 knockdown significantly suppresses PDAC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, circFOXP1 acts as a molecular sponge for miR-320b, leading to the upregulation of epidermal growth factor receptor (EGFR) ligand Epiregulin (EREG) and the subsequent activation of the MAPK/ERK signalling pathway, which is crucial for maintaining the aggressive phenotype of PDAC. The blockade of EREG using neutralizing antibodies in vivo substantially abrogates circFOXP1-induced tumorigenesis. Our findings underscore the potential of circFOXP1 as a novel biomarker and propose a novel therapeutic target to improve survival in PDAC patients.