Heme oxygenase 1 (HO-1) up-regulation drives cell adaptation to different stressors. Previous works from our lab have shown that HO-1 plays a crucial role in neuroblastoma cells (NB) response to oxidative stress (OS), but also demonstrated that sensitivity to OS increases after retinoic acid-induced NB-differentiation.

In this study, we evaluated the involvement of the molecular mechanisms of HO-1 induction in NB cell response to OS, analyzing its main activator Nrf2 and its main repressor Bach1.

We showed that retinoic acid-differentiated NB cells are more susceptible to OS as they reduce the ability to up-regulate HO-1. We demonstrated that Bach1 displacement from HO-1 promoter in undifferentiated cells enables the binding of Nrf2, while in differentiated cells, Bach1 displacement was impaired preventing Nrf2 binding and HO-1 induction.

Furthermore, we considered the role played by miRNA494, which could be involved in Bach1 post-transcriptional regulation. Preliminary data showed that miRNA494 is down-regulated in differentiated cells and that its inhibition in undifferentiated cells increases sensitivity to OS.

In conclusion, this study highlights the role of Bach1 in the regulation of HO-1 in NB cell response to OS.

This is one of the scientific articles published by one or more synbrAIn collaborators and data scientists.

If you are interested in learning more, read the entire article here.