Fig. 4.

YTHDC2 suppressed cystine uptake dependent on SLC7A11. (A, B) SLC7A11 protein and mRNA expression in H1299 control cells, YTHDC2^WT and YTHDC2^ΔYTH overexpression cells, as determined by IB and RT-qPCR assay. (C, D) IHC and RT-qPCR assay showed Slc7a11 expression in KPE, KPY^WT and KPY^ΔYTH tumor tissues (n = 30 tumors from 8 mice per group), scar bar 50 μm. (E–G) SLC7A11 protein expression, mRNA level and cystine uptake were measured in H1299 control cells, YTHDC2^WT overexpression cells with or without simultaneously overexpressed SLC7A11, as detected by IB, RT-qPCR and L-¹⁴C-cystine (0.2 μCi/mL). (H–J) SLC7A11 protein expression, mRNA level and cystine uptake were measured in H1299 control cells, ATF4 overexpression cells with or without simultaneously overexpressed YTHDC2^WT, as detected by IB, RT-qPCR and L-¹⁴C-cystine (0.2 μCi/mL). (K–M) Representative IHC images of YTHDC2 and SLC7A11 expression from two paired LUAD cases in corhort#1 TMA (K), scar bar 200 μm. Proteins were quantified by IHC scores (L). And the correlation between YTHDC2 protein and SLC7A11 protein level in cohort#1 (pearson analysis, p = 0.0002) (M). Statistical analysis was performed using one-way ANOVA (B, D, F, G, I, J) Chi-squared test (L). Data are means ± SEMs, **p < 0.01, N·S.: no significant.