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

Glioma is characterized by high migration and invasion, and the relative molecular mechanism is still poor. Accumulating studies demonstrated that ubiquitin specific protease 39 (USP39) played an oncogenic role in several cancers. Here, we investigate USP39 expression and function in human glioma. Oncomine database analysis revealed high USP39 expression in glioma and elevated USP39 expression correlated significantly with poor overall survival. Knockdown of USP39 significantly inhibited the migration and invasion of U251 and U87 cells. The gene expression profile was executed to screen the target molecules of USP39. The result showed that ADAM9, a molecule involved in migration and invasion of various human tumors, was significantly downregulated in the U251 and U87 cells with shRNA-mediated USP39 knockdown. Mechanistically, USP39 directly interacted with the ADAM9 mRNA and induced ADAM9 mRNA maturation, following the decreased expression of integrin β1. Besides, overexpressed ADAM9 rescued the inhibited migration and invasion of glioma cells causing by USP39 depletion. USP39 promoted invasion in vivo and reduced the overall survival of the mice. Collectively, USP39 may have oncogenic role that increase ADAM9 protein levels by inducing maturation of ADAM9 mRNA in glioma. USP39 could be considered a new potential therapeutic target for glioma. Human glioma cell line U87 were infected with lentiviruses encoding USP39-targeting or negative control shRNA (shUSP39 or shNA) , cells with stable knockdown USP39 or negative control were screened by GFP and puromycin.