Taken together, our research identified a functional positive feedback loop of the miR-548ac/YB-1/Snail axis, which could be the trigger under acidic microenvironment, contributing to the endothelial to mesenchymal transition of HUVECs, further led to a significant increase of endothelial cell permeability, consequently facilitated the malignant progression of pancreatic cancer. This evidence concerns the gene YBX1 and familial pancreatic carcinoma.