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Updated: Feb 25, 2026

Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing
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Published on: June 9, 2017

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miR-432 Induces NRF2 Stabilization by Directly Targeting KEAP1

Burak Akdemir1, Yasuaki Nakajima2, Johji Inazawa3,4

  • 1Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.

Molecular Cancer Research : MCR
|August 2, 2017
PubMed

Insights

MicroRNA-432-3p enhances cancer cell survival by downregulating KEAP1, leading to NRF2 activation and reduced sensitivity to chemotherapy drugs like cisplatin in esophageal squamous cell carcinoma.

Area of Science:

  • Molecular biology
  • Cancer research
  • Gene regulation

Background:

  • NF-E2-related factor 2 (NRF2) is a key regulator of cellular stress responses, typically inhibited by Kelch-like ECH-associated protein 1 (KEAP1).
  • Aberrant NRF2 stabilization in cancer promotes tumor growth and chemoresistance.
  • MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression, but their role in the NRF2-KEAP1 pathway is not well understood.

Purpose of the Study:

  • To investigate the role of microRNA-432-3p (miR-432-3p) in regulating the NRF2-KEAP1 pathway.
  • To determine the impact of miR-432-3p on chemoresistance in esophageal squamous cell carcinoma (ESCC).

Main Methods:

  • Investigated the direct binding of miR-432-3p to KEAP1 mRNA.
  • Assessed the effect of miR-432-3p overexpression and inhibition (using CRISPR/Cas9) on NRF2 activity and chemoresistance in ESCC cells treated with cisplatin (CDDP).
  • Analyzed miR-432-3p and KEAP1 expression levels in primary ESCC tumors.

Main Results:

  • miR-432-3p directly binds to KEAP1 mRNA, leading to its downregulation and subsequent NRF2 activation.
  • Overexpression of miR-432-3p decreased ESCC cell sensitivity to cisplatin, while its inhibition increased sensitivity.
  • miR-432-3p was found to be overexpressed in a majority of ESCC tumors, with an inverse correlation to KEAP1 expression.

Conclusions:

  • miR-432-3p positively regulates NRF2 activity by targeting KEAP1.
  • This miRNA-mediated regulation contributes to chemoresistance in esophageal squamous cell carcinoma.
  • The findings elucidate a novel mechanism of NRF2 stabilization in cancer and suggest miR-432-3p as a potential therapeutic target.

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