The level of HOTAIR expression in GBM was higher than in other low grade gliomas and normal brain tissues. NLK (Nemo-like kinase), a negative regulator of the B-catenin pathway, was negatively correlated with HOTAIR expression. When the B-catenin pathway was inhibited, GBM cells became susceptible to cell cycle arrest and inhibition of invasion. Introduction of the HOTAIR 5' domain in human glioma-derived astrocytoma induced B-catenin. An intracranial animal model was used to confirm that HOTAIR depletion inhibited GBM cell migration/invasion. In the orthotopic model, HOTAIR was required for GBM formation in vivo.