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Updated: Jul 19, 2025

Using the E1A Minigene Tool to Study mRNA Splicing Changes
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NRF2 has a splicing regulatory function involving the survival of motor neuron (SMN) in non-small cell lung cancer

Qinqin Cui1, Wei Wang1, Akhileshwar Namani1

  • 1Department of Biochemistry and Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, P. R. China.

Oncogene
|August 12, 2023
PubMed

Insights

Nuclear factor erythroid 2-like 2 (NRF2) regulates RNA splicing, impacting cancer. This study reveals NRF2

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • The nuclear factor erythroid 2-like 2 (NFE2L2; NRF2) pathway is often dysregulated in human cancers.
  • Non-transcriptional roles of NRF2 in cancer, particularly in RNA processing, are largely unexplored.
  • Understanding NRF2's functions beyond transcriptional activation is crucial for cancer therapy development.

Purpose of the Study:

  • To investigate the role of NRF2 in regulating RNA splicing.
  • To elucidate the molecular mechanisms underlying NRF2-mediated splicing control.
  • To explore the therapeutic implications of targeting the NRF2 pathway in cancer.

Main Methods:

  • Global alternative splicing analysis in NRF2-knockdown non-small cell lung cancer (NSCLC) cells.
  • Mechanistic studies involving NRF2 binding to the SMN1 promoter and protein-protein interactions.
  • Functional rescue experiments in NRF2-knockout cells and analysis of patient data (The Cancer Genome Atlas).

Main Results:

  • NRF2 knockdown altered 839 alternative splicing events in 485 genes in NSCLC cells.
  • NRF2 directly regulates SMN mRNA expression and interacts with SMN protein in nuclear bodies.
  • SMN overexpression correlates with NRF2 pathway alterations in lung squamous cell carcinoma patients.

Conclusions:

  • NRF2 plays a significant, previously unrecognized role in regulating RNA splicing.
  • The NRF2-SMN interaction is a key mechanism controlling RNA splicing.
  • Targeting the NRF2 pathway offers a potential novel therapeutic strategy for cancers with aberrant NRF2 signaling.

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