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Heparanase (HPSE) is the endogenous endoglycosidase that degrades heparan sulfate proteoglycans and promotes the tumor growth, invasion, metastasis, and angiogenesis. Our previous studies have shown that HPSE is highly expressed in neuroblastoma (NB), the most common extracranial solid tumor in childhood. However, the underlying regulatory mechanisms remain largely unknown. In this study, we identified one binding site of microRNA-558 (miR-558) within the HPSE promoter. In NB tissues and cell lines, miR-558 was up-regulated and positively correlated with HPSE expression. Gain- and loss-of-function studies demonstrated that miR-558 facilitated the transcript and protein levels of HPSE and its downstream gene, vascular endothelial...

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