NFE2L2 and central nervous system cancer: There are evidences showing that HACE1 reduces oxidative stress by activating NRF2,17 and NRF2 accelerates malignant transformation and progression of glioma by its anti-oxidative stress function.18,19 This was strongly supported by our data and the Cancer Genome Atlas (TCGA) database showing that NRF2 was significantly elevated in gliomas compared with control subjects (Supplementary Fig. S5a, b), and high NRF2 expression was strongly related to poor patient survival (Supplementary Fig. S5c).