Ubiquitin-specific peptidase 39 promotes human glioma cells migration and invasion by facilitating ADAM9 mRNA maturation.

Glioma cells are characterized by high migration and invasion ability, however the molecular mechanism behind both processes still remain to be investigated. Several studies have demonstrated that ubiquitin specific protease 39 (USP39) plays an oncogenic role in various cancer types. Here, we investigated the expression and function of USP39 in patients with glioma. Oncomine database analysis revealed that high USP39 expression significantly correlated with poor overall survival in patients with glioma. Knockdown of USP39 in U251 and U87 cell lines significantly inhibited their migration and invasion in vitro. Gene expression profiling of glioma cells transduced with shRNA against USP39 revealed that ADAM9, a molecule previously related to tumor cell migration and invasion, was significantly downregulated. Further on, USP39 induced ADAM9 mRNA maturation and decreased the expression of integrin β1. Additionally, overexpression of ADAM9 inhibited the migration and invasion of glioma cells caused by USP39 depletion in vitro. USP39 promoted the invasion of glioma cells in vivo and reduced the overall survival of the mice. Altogether, our data shows that USP39 induces mRNA maturation and elevates the expression of ADAM9 in glioma cells and may thus be considered as potential target for treating patients with glioma.