In contrast, miR-181a is considered a CS oncogene, as it is overexpressed in high-grade CS, is upregulated by hypoxia, and increases vascular endothelial growth factor (VEGF) expression by targeting regulator of G-protein signaling 16 (RGS16), a negative regulator of CXC chemokine receptor 4 (CXCR4) signaling46. This evidence concerns the gene CXCR4 and Cowden syndrome 1.