In this study, we confirmed high CRNDE expression in clinical glioma specimens and observed through experiments in human glioma cell lines a novel molecular mechanism by which CRNDE may contribute to glioma pathogenesis. By inducing or silencing CRNDE expression, we detected a positive correlation between CRNDE levels and the proliferative, migratory, and invasive capacities of glioma cells, which were concomitant with a decreased apoptosis rate. Our experiments also suggest that these effects are mediated by downregulation of miR-136-5p, which correlated with the glioma WHO grade. Based on predicted CRNDE/miR-136-5p/mRNA interactions, both the mRNA and protein expression analyses suggested that miR-136-5p-mediated repression of Bcl-2 and Wnt2 underlies the pro-tumoral actions of CRNDE. We therefore propose that CRNDE functions as a competing endogenous RNA (ceRNA) that binds to and negatively regulates miR-136-5p, thereby protecting Bcl-2 and Wnt2 from miR-136-5p-mediated inhibition in glioma.