Because Spry2 protein levels are decreased in hepatocellular carcinomas [24–28] and given the opposite actions of Spry2 and HIF1α/HIF2α on cell proliferation and migration [15,16,19,36,37,48–53], we performed an in silico analysis of the SPRY2 promoter for hypoxia response elements (HRE) with the consensus sequence 5’-A/GCGTG-3’ and found 10 putative HREs; five in the proximal promoter and five in the first intron. Here, EPAS1 is linked to hepatocellular carcinoma.