GLI1 is involved in HIF-1α-induced migration, invasion, and epithelial-mesenchymal transition in glioma cells.

INTRODUCTION: Glioma is characterized by hypoxia that activates the hypoxia inducible factor (HIF) pathway and controls a myriad of genes that drive cancer progression. HIF-1α promotes GLI1 transferring to the nucleus by activating the hedgehog pathway under hypoxic conditions. However, their mechanisms in glioma cells under hypoxia remain unknown.

MATERIAL AND METHODS: Human glioma cell lines (LN229 and LN18) were transfected with HIF-1α or GLI1-specific short hairpin RNAs (shRNAs) and cultured under normoxic or hypoxic conditions. The protein levels of HIF-1α, GLI1, and epithelial-mesenchymal transition (EMT) markers including E-cadherin and vimentin were measured by Western blot analysis. RT-qPCR analysis was performed for the detection of HIF-1α and GLI1 mRNA expression. Cell migratory and invasive capacities were evaluated by wound healing and Transwell assays, respectively.

RESULTS: Hypoxia blocked the breakdown of the HIF-1α protein and upregulated GLI1 expression in glioma cells. Downregulation of HIF-1α expression inhibited hypoxia-induced cell migration and invasion, as well as reversed the effects of hypoxia on GLI1, E-cadherin, and vimentin expression in LN229 and LN18 cells. Depletion of GLI1 inhibited glioma cell migration and invasion induced by hypoxia. Silenced GLI1 did not affect HIF-1α expression but completely offset hypoxia-regulated expression of E-cadherin and vimentin in glioma cells.

CONCLUSIONS: GLI1 is involved in HIF-1α-induced migration, invasion, and EMT in glioma cells, thus revealing a novel molecular mechanism for glioma research.