Fig. 3: HIF-2α activates UPRER via regulating SOD2-mtROS axis.

A The mRNA level of SOD2 and SOD1 were detected in HIF-2α OE MCF7 cells and HIF-2α KD MCF7 MS cells. B The correlation between HIF-2α and SOD2 was detected in mRNA level from TCGA database (n = 1169). C The mRNA expression of SOD2 was compared in CD44+CD24− and non CD44+CD24− patients from TCGA database (n = 1169). D The levels of mtROS were detected in MCF7 and MCF7 MS cells, HIF-2α OE MCF7 cells and HIF-2α KD MCF7 MS cells. E The mRNA level of SOD2 and mtROS level were measured in SOD2-overexpressing and HIF-2α-silencing (SOD2 OE + HIF-2α KD) MCF7 MS cells, under 1% O2. F The mRNA level of SOD2 and mtROS level were measured in HIF-2α KD MCF7 MS cells cultured with mitoTEMPOL (100 µM) for 48 h, under 1% O2. G The self-renewal ability rescued in HIF-2α KD MCF7 MS cells cultured mitoTEMPOL (100 µM) for 48 h, compared with HIF-2α KD MCF7 MS cells, under 1% O2. Scale bar, 250 μm. H The cells viability rate was detected in HIF-2α KD MCF7 MS cells cultured with mitoTEMPOL (100 µM) for 48 h, under 1% O2. I The expression level of GRP78 was detected in HIF-2α KD MCF7 MS cells cultured with mitoTEMPOL (100 µM) for 48 h, under 1% O2. NS, non-significant; *P < 0.05, **P < 0.01, ***P < 0.001, compared to MCF7 cells/Ctrl/shCtrl/shHIF-2α; Student’s t test, two-way ANOVA test, Mann–Whitney U analysis, Pearson correlation analysis. Error bars, mean ± SD (n = 3).