Collectively, we conclude that METTL3 and METTL14-mediated m6A modifications were crucial for sustaining the high-expressed status of miR-380-3p in PC cells and tissues, and upregulation of miR-380-3p degraded PTEN to activate the tumor-promoting Akt pathway, resulting in the aggressiveness of PC. This evidence concerns the gene METTL14 and pachyonychia congenita.