Additionally, microRNA participates in this resistance network, such as miR-15b downregulates Smurf2 to inhibit Smad2/3 ubiquitination and degradation, thereby activating the TGF-β-induced EMT and driving resistance in PC in vitro289, while MiR-223 downregulates FBW7 to exacerbate EMT and resistance in GEM-resistant PC in vitro209. This evidence concerns the gene SMAD2 and pachyonychia congenita.