Fig. 6. The novel mechanism by which HIF1α and HIF2α regulate the malignant progression of GBM through miR-210-3p and EGF.

HIF1α and HIF2α mutually regulate each other through a negative feedback loop mediated by miR-210-3p, and high levels of miR-210-3p lead to higher HIF1α expression. HIF1α and HIF2α are upstream regulators of the transcription of the EGF gene, which regulates GBM malignancy through the related signalling pathway activated by EGF. In summary, HIF1α/HIF2α-miR-210-3p are critical factors that contribute to GBM growth, dedifferentiation and chemoresistance by regulating pathways activated by EGF in hypoxic cells, thus increasing GBM malignancy.