circACTR2 overexpression reversed the chemoresistance of PC cells to GEM through inhibiting PI3K/AKT signaling pathway by sponging miR-221-3p and upregulating PTEN expression (Fig. 7), which might provide an essential hint for circACTR2 as therapeutic target to overcome PC cheomresistance. Here, AKT1 is linked to pachyonychia congenita.