RESUMO
Myeloid ecotropic virus insertion site 1 (MEIS1) is a HOX co-factor necessary for organ development and normal hematopoiesis. Recently, MEIS1 has been linked to the development and progression of various cancers. However, its role in gliomagenesis particularly on glioma stem cells (GSCs) remains unclear. Here, we demonstrate that MEIS1 is highly upregulated in GSCs compared to normal, and glioma cells and to its differentiated counterparts. Inhibition of MEIS1 expression by shRNA significantly reduced GSC growth in both in vitro and in vivo experiments. On the other hand, integrated transcriptomics analyses of glioma datasets revealed that MEIS1 expression is correlated to cell cycle-related genes. Clinical data analysis revealed that MEIS1 expression is elevated in high-grade gliomas, and patients with high MEIS1 levels have poorer overall survival outcomes. The findings suggest that MEIS1 is a prognostic biomarker for glioma patients and a possible target for developing novel therapeutic strategies against GBM.
RESUMO
Glioblastoma multiforme (GBM) is the most fatal form of brain cancer in humans, with a dismal prognosis and a median overall survival rate of less than 15 months upon diagnosis. Glioma stem cells (GSCs), have recently been identified as key contributors in both tumor initiation and therapeutic resistance in GBM. Both public dataset analysis and direct differentiation experiments on GSCs have demonstrated that CREB5 is more highly expressed in undifferentiated GSCs than in differentiated GSCs. Additionally, gene silencing by short hairpin RNA (shRNA) of CREB5 has prevented the proliferation and self-renewal ability of GSCs in vitro and decreased their tumor forming ability in vivo. Meanwhile, RNA-sequencing, luciferase reporter assay, and ChIP assay have all demonstrated the closely association between CREB5 and OLIG2. These findings suggest that targeting CREB5 could be an effective approach to overcoming GSCs.