HIC1 and neoplasm: NRF2 induces the degradation of tumor-suppressor genes, such as p53 or HIC1, through direct interactions between tumor-suppressor genes and NRF2 downstream target genes.36, 37 We confirmed that SIRT1 was transcriptionally regulated by the inhibition of activity or the knockdown of NRF2. As shown in Figure 5a, OTA treatment at doses of 1 or 10 μM reduced the mRNA levels of HO-1, NQO-1, and SIRT1 dose dependently in EP MSCs.