First, we examined the microvessel density in primary tumors by IHC assays and found that the decreased microvessel density by VHL overexpression was restored by overexpressed UBE3B in MDA-MB-231 tumors (Fig. 4D, G), and the increased microvessel density by VHL knockdown was partially but significantly abolished by UBE3B depletion (Fig. S4D, G), suggesting a critical role of VHL-UBE3B axis in breast tumor angiogenesis. This evidence concerns the gene VHL and breast neoplasm.