Modulation of Nrf2 expression by targeting i-motif DNA
2025

Controlling Nrf2 Expression by Targeting i-Motif DNA

Sample size: 1584 publication Evidence: moderate

Author Information

Author(s): Warner E. F., Guneri D., O’Connell M. A., MacDonald C. J., Waller Z. A. E.

Primary Institution: University of East Anglia, Norwich, Norfolk UK

Hypothesis

The i-motif-forming sequence downstream of the Nrf2 promoter may regulate the expression of the gene.

Conclusion

The study identified ligands that can modulate Nrf2 gene expression by targeting an i-motif structure in its promoter.

Supporting Evidence

  • The Nrf2 i-motif was found to be stable at near-physiological conditions.
  • Eleven ligands were identified that can bind to the i-motif structure.
  • One ligand significantly upregulated Nrf2 mRNA expression in human cancer cells.
  • Another ligand reduced Nrf2 mRNA expression in the same cells.

Takeaway

Scientists found a special part of DNA that can help control a gene important for fighting cancer, and they discovered some tiny molecules that can change how this gene works.

Methodology

The study used circular dichroism, UV spectroscopy, and NMR to characterize the i-motif and a high-throughput fluorescent indicator displacement assay to identify ligands.

Limitations

The study primarily focused on a specific cancer cell line and may not generalize to all types of cancer.

Statistical Information

P-Value

p≤0.001

Statistical Significance

p≤0.001

Digital Object Identifier (DOI)

10.1038/s42004-024-01387-w

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