Figure 1. TRAIL is a HIF2α target and a candidate synthetic essential gene.
A. Venn diagram between HIF2α-upregulated genes (logFC(Ctrl/sgEPAS1) > 1.5, FDR < 0.05) and DepMap preferentially essential genes (gene effect < 0, Z-score < −1) in 786O. B. Bubble plot of the 57 overlapped genes. The bubbles’ size and color reflect the false discovery rate (FDR) and Z-score, respectively. TRAIL has lowest Z-score and is highlighted. C. Relative mRNA expression of EPAS1 and TNFSF10 in control and HIF2α-knockout 786O sublines (n=3), measured with qRT-PCR. D. Immunoblotting of HIF2α and TRAIL in control and HIF2α-knockout 786O sublines. E. Relative mRNA expression of TNFSF10 in normal (n=161) and tumor tissues (n=532) of TCGA KIRC patient’s cohort. F. TRAIL protein expression in normal (n=84) and tumor tissues (n=110) of CPTAC KIRC patient’s cohort. G. Scatter plot of TNFSF10 and EPAS1 levels in the TCGA KIRC cohort. Spearman correlation coefficient ρ and P value are marked. H. HIF2α and input ChIP-Seq signals in the TNFSF10 locus with the promoter region chr3:172,242,513 – 172,243,623 highlighted in the red box. I. ChIP-qPCR result for IgG and anti- HIF2α at the TNFSF10 promoter (n=3).
In C and I, data represent mean ± SEM. Unpaired t-test for C and I, Mann-Whitney test for E and F, **P<0.01, ***P<0.001, ****P<0.0001.
