TBL2 modulates glioblastoma progression by inducing autophagy through by the AMPK/mTOR signaling pathway

Glioblastoma (GBM) is the most common primary malignant brain tumor in the central nervous system. The role of autophagy in GBM is highly complex, as it can promote both tumor cell survival and suppression of tumor progression. TBL2 is aberrantly expressed in various cancers and has been closely associated with tumor initiation and progression. This study aims to elucidate the role of TBL2 in GBM. Bioinformatics analysis of The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were performed to evaluate TBL2 expression. Quantitative real-time PCR (qRT-PCR) and Western blot was used to validate TBL2 expression in GBM cells. The biological functions of TBL2 in GBM progression (including cell proliferation, apoptosis, migration, and invasion) were assessed using siRNA-mediated knockdown of TBL2. Additionally, autophagy regulation was examined to explore the potential mechanisms through which TBL2 influences GBM progression. Our results demonstrated that knockdown of TBL2 significantly inhibited GBM cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while promoting apoptosis. Moreover, TBL2 silencing enhanced autophagy via the AMPK/mTOR signaling pathway. Further investigations revealed that AMPK activation augmented the inhibitory effects of TBL2 silencing on GBM cell migration, invasion, and EMT, and promoted apoptosis. Conversely, inhibition of autophagy with chloroquine attenuated the suppressive effects of TBL2 knockdown on GBM cell proliferation, migration, invasion, and EMT. In conclusion, this study identifies a novel regulatory mechanism through which TBL2 promotes GBM progression by modulating autophagy via the AMPK/mTOR pathway. These findings suggest that TBL2 may represent a potential therapeutic target for GBM.