Fig. 4: YAP promotes methionine uptake by upregulating SLC43A2 expression. | Nature Communications

Fig. 4: YAP promotes methionine uptake by upregulating SLC43A2 expression.

From: Positive feedback between arginine methylation of YAP and methionine transporter SLC43A2 drives anticancer drug resistance

Fig. 4

a, b The methionine concentration in Huh-7 cells (a) and HCT 116 cells (b) infected with YAP lentivirus for 96 h. c Schematic diagram for RNA sequence analysis. Seven-week-old mice were injected with AAV8-TBG-YAP-S127A through tail vein. 8 weeks later, the primary hepatocytes were isolated for RNA sequence analysis. d Heatmap from the RNA sequence analysis depicts different gene expression of transporters mediating methionine uptake and enzymes involving in methionine metabolism. e, f The mRNA levels of SLC family in Huh-7 cells (e) and HCT 116 cells (f) infected with YAP lentivirus for 96 h. g The methionine concentration in Huh-7 cells transfected with indicated siRNAs for 48 h. h The protein level of SLC43A2 in Huh-7 cells and HCT 116 cells infected with YAP lentivirus for 96 h. The data represents the relative ratio of SLC43A2 to GAPDH. i Spearman correlation between YAP and SLC43A2 in HCC tumors and normal tissues in TCGA dataset. j Kaplan–Meier overall survival analysis of SLC43A2 for HCC patients in TCGA dataset. k The mRNA expression of SLC43A2 in Huh-7 cells transfected with YAP or YAP-S94A plasmids for 72 h. l The mRNA expression of SLC43A2 in Huh-7 cells transfected with YAP and/or si-TEAD4 for 72 h. m, n ChIP-qPCR assays in Huh-7 cells with YAP (m) and TEAD4 (n) antibody showed the binding of YAP-TEAD4 to the promoter of SLC43A2. o Luciferase activity in 293 T cells transfected with YAP. The SLC43A2 luciferase reporters expressing wild-type or mutated TEAD binding sites (Mut1, Mut2, Mut1 + 2) were used. Statistical analyses were performed using two-sided unpaired Student’s t-test (a, b, e, f), one-way ANOVA with multiple comparisons (g, k, l–o), two-tailed Spearman’s correlation test (i) or Kaplan–Meier analysis (Mantel–Cox test, j). Data were presented as mean ± SD. n = 3 (a, b, d–g, k, l) or 4 (m–o) biologically independent samples. The data presented in (h) are representative of three independent experiments. Source data are provided as a Source Data file.

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