SREBP2/Rab11s/GLUT1/6 network regulates proliferation and migration of glioblastoma.

Abstract

Cholesterol serves a vital role in the occurrence and development of glioblastoma multiforme (GBM). Furthermore, cholesterol synthesis is regulated by sterol regulatory element-binding protein 2 (SREBP2), and certain glucose transporters (GLUTs) and Ras-related protein Rab11 (Rab11) small GTPase family members (Rab11s) may contribute to the process. The Cancer Genome Atlas was used to analyze the relationship between prognosis and GLUT gene expressions. To investigate the regulatory effect of Rab11s and SREBP2 on GLUTs during tumor progression, single cell RNA sequencing (scRNA-seq), western blotting and reverse transcription-quantitative PCR were performed on glioma tissues and the T98G GBM cell line. Cell viability and migration were assessed by performing MTT and wound healing assays, respectively. Moreover, the dual-luciferase reporter gene assay was conducted to predict the sterol regulatory elements in the promoter regions of the target genes. The results demonstrated that high SREBP2, GLUT1 and GLUT6 expression was associated with poor survival of patients with GBM. ScRNA-seq distinguished glioblastoma cells by EGFR and indicated the related lipid metabolism signaling pathways. Moreover, the results indicated that GLUT1 and GLUT6 were regulated by SREBP2 and Rab11s. Rab11s and SREBP2 also contributed to T98G cell viability and migration. Additionally, the results indicated that Rab11s, GLUT1 and GLUT6 were transcriptionally regulated by SREBP2. Therefore, the present study suggested that the SREBP2/Rab11/GLUT network promoted T98G cell growth, thus, identifying potential therapeutic targets for GBM.