Expression analysis and regulation of GLI and its correlation with stemness and metabolic alteration in human brain tumor

GLI gene-mediated hedgehog (Hh) signaling pathway plays a substantial role in brain cancer development and growth including glioblastoma multiforme (GBM), lower-grade glioma (LGG), and medulloblastoma (MB). GLI2 and GLI3 gene expression levels are extremely enhanced in these cancers with poor patient survival. Moreover, GLI genes are correlated with stemness-related factors SOX2, SOX9, POU5F1, and NANOG that work as the driving factors for brain cancer stem cells (CSCs) progression. It's critical to find new ways to combat this deadly malignancy and CSCs. Using in silico approaches, our study explored the role of GLI genes (GLI1, GLI2, and GLI3), the primary transcription factors of the sonic hedgehog (SHH) signaling pathway, in GBM, LGG, MB, and glioblastoma stem-like cells (GSCs). Additionally, we found strong association of angiogenic-related gene VEGFA, metabolic genes ENO1, ENO2, and pluripotency-related genes SOX2, SOX9, NANOG, POU5F1 with GLI genes, suggesting their role in brain tumor initiation and progression. We also studied their transcriptional network and functional category enrichment analysis about brain tumor development to find a better therapeutic strategy against brain cancer and their stem cells.