LncRNA NEAT1 promotes malignant phenotypes and TMZ resistance in glioblastoma stem cells by regulating let-7g-5p/MAP3K1 axis.

Glioblastoma (GBM) is one of the most malign brain tumors in adults. Temozolomide is an oral chemotherapy drug constituting the backbone of chemotherapy regimens utilized as first line treatment of glioblastoma. However, resistance to TMZ often leads to treatment failure. In this study, we explored the expression and related mechanisms of NEAT1 in glioma stem cells (GSCs). Quantitative real-time PCR (qRT-PCR) showed that NEAT1 was upregulated in serum samples of GBM patients and GSCs isolated from U87, U251 cell lines. Functional experiments showed that NEAT1 knockdown restrained malignant behaviors of GSC, including proliferation, migration and invasion. Dual-luciferase assays identified let-7g-5p was a down-stream target and negatively adjusted by NEAT1. Restoration of let-7g-5p impeded tumor progression by inhibiting proliferation, migration and invasion. MAP3K1, as a direct target of let-7g-5p, was positively regulated by NEAT1 and involved to affect the regulation of NEAT1 on GSCs behaviors. In conclusion, our results suggest that NEAT1 promoted GSCs progression via NEAT1/let-7g-5p/MAP3K1 axis, which provide a depth insight of TMZ resistance mechanism.