CRISPRi-mediated suppression of RPTOR and RICTOR inhibits Glioblastoma Cell Growth

ABSTRACT: Glioblastoma multiforme (GBM) is the most aggressive brain tumor and is associated with a poor prognosis. The mTOR pathway plays a critical role in GBM biology by integrating growth and metabolic signals through two functionally distinct complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), regulated by RPTOR and RICTOR, respectively. Although both complexes have been implicated in GBM progression, their relative contributions to GBM remain largely unknown. Here, we used CRISPR interference (CRISPRi) to suppress RPTOR and RICTOR individually and in combination and evaluated their effects on GBM. RPTOR suppression markedly reduced cell number, cell viability, cell migration and invasion, whereas RICTOR suppression alone produced comparatively limited effects. However, RICTOR suppression further enhanced the effect of RPTOR suppression on cell migration. Transcriptomic profiling of RPTOR and RICTOR knockdown in GBM cells identified 1,216 differentially expressed genes with significant enrichment for mTORC1 signaling, hypoxia, glycolysis, cholesterol homeostasis, fatty acid metabolism and oxidative phosphorylation pathways. Together, our results identify RPTOR as the major contributor to GBM cell phenotypes, reveal broad mTOR-associated metabolic transcriptional remodeling following combined RPTOR and RICTOR suppression and provide a potential therapeutic target for GBM.

ORGANISM(S): Homo sapiens

PROVIDER: GSE352797 | GEO | 2026/11/01

REPOSITORIES: GEO