miR-1285 is significantly downregulated in GEM-PC cell lines. In vitro experiments demonstrate that miR-1285 inhibits PC cell proliferation, migration, and invasion while increasing sensitivity to GEM. Western blotting analysis reveals that miR-1285 negatively regulates YAP1 protein levels, which, in conjunction with EGFR and β-catenin, modulates the biological behavior of PDAC cells. This evidence concerns the gene EGFR and pachyonychia congenita.