Fig. 2: R124 asymmetric dimethylation of YAP promotes YAP-related drug resistance.

a, b The relative YAP-TEAD activity in Huh-7 cells treated with the indicated concentration of sorafenib (a) and HCT 116 cells treated with the indicated concentration of oxaliplatin (b). c, d The relative expression of YAP target genes in Huh-7 cells treated with sorafenib (0.75 μM) (c) and HCT 116 cells treated with oxaliplatin (4 μM) (d) for 72 h. e, f The level of YAP R124me2a in Huh-7 cells treated with sorafenib (0.75 μM) (e) and HCT 116 cells treated with oxaliplatin (4 μM) (f). The data represents the relative ratio of YAP R124me2a to YAP. g The cell viability of YAP-, YAP-R124K-, YAP-S127A-, or YAP-R124F-overexpressed Huh-7 cells treated with sorafenib for 24 h. h The cell viability of YAP-, YAP-R124K-, YAP-S127A-, or YAP-R124F-overexpressed HCT 116 cells treated with oxaliplatin for 48 h. i Kaplan–Meier analysis of overall survival in a cohort of 191 hepatocellular carcinoma patients presenting a low level of YAP R124me2a (left panel) or high level of YAP R124me2a (right panel), who were treated with or without sorafenib. Statistical analyses were performed using one-way ANOVA with multiple comparisons (a–d, g, h) or Kaplan–Meier analysis (Gehan-Breslow-Wilcoxon test, i). Data were presented as mean ± SD. n = 4 (a) or 3 (b–d, g, h) biologically independent samples (a–d, g, h). The data presented in (e, f) are representative of three independent experiments. Source data are provided as a Source Data file.