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Targeting the KEAP1/NRF2 pathway to manipulate the expression of oncogenic and oncosuppressive miRNAs in human

Kristian M Bowles1,2, Stuart A Rushworth1

  • 1Department of Molecular Haematology; Norwich Medical School; University of East Anglia; Norwich, United Kingdom.

Molecular & Cellular Oncology
|September 26, 2018
PubMed

Insights

The nuclear factor E2-related factor 2 (NRF2) pathway regulates microRNAs in acute myeloid leukemia (AML). This finding adds to the known prosurvival functions of NRF2 in cancer.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Signaling

Background:

  • The Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor E2-related factor 2 (NRF2) pathway is crucial for cellular defense against oxidative stress.
  • Dysregulation of the NRF2 pathway is implicated in various cancers, including acute myeloid leukemia (AML).

Purpose of the Study:

  • To investigate the role of NRF2 in regulating microRNA expression in acute myeloid leukemia.
  • To explore novel prosurvival functions of NRF2 in the context of AML.

Main Methods:

  • Analysis of NRF2-mediated gene expression in AML cells.
  • Quantitative assessment of microRNA-125B and microRNA-29B levels.

Main Results:

  • NRF2 was found to modulate the expression of microRNA-125B and microRNA-29B in acute myeloid leukemia.
  • This regulation represents a newly identified prosurvival mechanism for NRF2 in leukemia.

Conclusions:

  • NRF2 plays a significant role in controlling microRNA expression within acute myeloid leukemia.
  • The modulation of microRNAs by NRF2 contributes to its prosurvival functions in leukemia, offering potential therapeutic targets.

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