Quantitative real-time PCR demonstrated that NEAT1 was upregulated in GSCs. NEAT1 knockdown inhibited GSC cell proliferation, migration and invasion and promoted GSC apoptosis. A potential binding region between NEAT1 and microRNA let-7e was confirmed by dual-luciferase assays. Upregulation of NEAT1 reduced the expression of let-7e, and there was reciprocal repression between NEAT1 and let-7e in an Argonaute 2-dependent manner. Let-7e expression was lower expression in glioblastoma tissues and GSCs than in normal brain tissues and cells. Restoration of let-7e suppressed tumor function by inhibiting proliferation, migration and invasion while promoting apoptosis in GSCs.