Knockdown of USP51 decreases DDP resistance in A549/DDP cells by modulating ZEB1 ubiquitination. (A) After infection of ZEB1/vector lentivirus in A549/DDP cells, ZEB1 mRNA and protein levels were detected. (B) A549/DDP cells were infected with shUSP51 and ZEB1 lentiviruses and treated with 100 µmol/l DDP, and apoptotic cells were detected. (C) ZEB1 mRNA expression in USP51-silenced A549/DDP cells was detected. (D) Interaction between USP51 and ZEB1 was determined by Co-Immunoprecipitation experiment. (E) Ubiquitin-mediated degradation of ZEB1 in USP51-silenced A549/DDP cells, as well as Zeb1 and USP51 protein, was examined by western blotting. *P<0.05 and ***P<0.001 vs. vector or DDP + vector + shNC, and ##P<0.01 vs. DDP + vector + shUSP51; and +++P<0.001 vs. DDP + ZEB1 + shNC. A549/DDP, DDP-resistant A549 cells. USP, ubiquitin-specific protease; ZEB1, zinc-finger E-box binding homeobox 1; sh, short hairpin RNA; NC, negative control.