Fig. 5: The positive feedback between YAP R124 methylation and SLC43A2 persists in drug resistance.

a, b The level of YAP R124 methylation in Huh-7 cells transfected with indicated siRNA and treated with sorafenib (0.75 μM) for 48 h (a) and HCT 116 cells (b) transfected with indicated siRNA and treated with oxaliplatin (4 μM) for 48 h. The data represents the relative ratio of YAP R124me2a to YAP. c Representative images of the level of SLC43A2 and YAP R124me2a in HCC tissues (left panel) and the clinical relevance between the level of SLC43A2 and YAP R124me2a was determined (right panel). n = 28. Scale bar = 50 μm. d, e The transcriptional levels of SLC43A2, YAP, and YAP target genes in Huh-7 cells (d) and HCT 116 cells (e) transfected with si-SLC43A2 for 72 h. f Heatmap from TCGA dataset analysis depicts differential expression of YAP target genes in HCC patients with high and low expression of SLC43A2. g, h The level of SLC43A2 in Huh-7 cells treated with sorafenib (0.75 μM) (g) and HCT 116 cells treated with oxaliplatin (4 μM) (h). The data represents the relative ratio of SLC43A2 to GAPDH. i The cell viability of YAP-, YAP-S127A-, or YAP-R124F-overexpressed Huh-7 cells treated with sorafenib and transfected with si-SLC43A2 for 24 h. j The cell viability of YAP-, YAP-S127A-, or YAP-R124F-overexpressed HCT 116 cells treated with oxaliplatin and transfected with si-SLC43A2 for 48 h. Statistical analyses were performed using two-tailed Spearman’s correlation test (c), two-sided unpaired Student’s t-test (d, e, g, h), or one-way ANOVA with multiple comparisons (i, j). Data were presented as mean ± SD. Data were presented as mean ± SD. n = 3 (d, e, g, h, i, j) or 28 (c) biologically independent samples. The data presented in (a, b, g, h) are representative of three independent experiments. Source data are provided as a Source Data file.