Figure 1: MYC and PVT1 regulation in renal cancer. | Nature Communications

Figure 1: MYC and PVT1 regulation in renal cancer.

From: Genetic variation at the 8q24.21 renal cancer susceptibility locus affects HIF binding to a MYC enhancer

Figure 1

(a) Analyses of TCGA renal cancer data sets indicate significant overexpression of MYC and PVT1 RNA in clear cell and papillary RCC. Box-and-whisker plots of normalized RNA-seq reads from matching normal (N) and tumour tissue (T) in clear cell (n=22), papillary (n=31) and chromophobe (n=25) RCC. Horizontal lines represent medians, whiskers the 5 and 95% percentiles and dots outliers. *Paired t-test, P<0.0001. (b) MYC and PVT1 RNA expression is reduced by pVHL re-expression in RCC4 renal cancer cells. HIF stabilization by DMOG induces expression of both genes specifically in RCC4 pVHL re-expressing cells. RCC4 cells with defective (blue) or functional (yellow) pVHL were exposed to vehicle or 1 mM of the HIF stabilizer DMOG for 16 h. n=3 from independent experiments; values are mean±s.d., *One-sample t-test, P<0.05. (c) Box-and-whisker plot of relative expression levels (fold change compared to untreated control) of MYC and PVT1 RNA in a collection of 10 pVHL-competent renal tubular derived cells (RCC, primary renal tubular and immortalized renal tubular cells, blue) and 10 non-tubular-derived cells (renal podocytes and non-renal cells, green) exposed to 1 mM DMOG for 16 h. For details of cell lines, please see Supplementary Fig. 2; horizontal lines represent median values and whiskers show the 5 and 95% percentiles; *Mann–Whitney U-test; P<0.05. (d) MYC protein levels are high in HIF-positive tumours. A total of 330 ccRCC tumours were stratified according to the immunoreactive score for HIF-1α, HIF-2α and MYC staining in no, low, medium or strong staining. Fractions of MYC signals are shown for each subgroup for HIF-staining. χ2-test; P<0.001 for both HIF-1α and HIF-2α. (e) MYC and PVT1 RNA expression in HIF-α depleted (si HIF 1α/2α, siRNA against HIF1α/2α) or control transfected (si dHIF, siRNA against drosophila HIF) RCC4 pVHL-competent cells exposed to vehicle (ctrl, black) or 1 mM DMOG (grey) for 16 h. Data present mean±s.d. from six independent experiments. *One-sample t-test, P<0.05).

Back to article page