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RNA-binding motif protein 47 inhibits Nrf2 activity to suppress tumor growth in lung adenocarcinoma

T Sakurai1, K Isogaya1, S Sakai1

  • 1Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Oncogene
|March 1, 2016
PubMed

Insights

RNA-binding motif protein 47 (RBM47) acts as a tumor suppressor by inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Loss of RBM47 promotes cancer progression and metastasis, highlighting its therapeutic potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • RNA-binding proteins regulate gene expression post-transcriptionally during cancer progression.
  • Transforming growth factor-beta (TGF-β) signaling influences epithelial-to-mesenchymal transition (EMT).

Purpose of the Study:

  • To investigate the role of RNA-binding motif protein 47 (RBM47) in cancer.
  • To elucidate the mechanism by which RBM47 affects cancer progression and its relationship with TGF-β and Nrf2 signaling.

Main Methods:

  • Identification of RBM47 as a TGF-β target gene in NMuMG cells undergoing EMT.
  • Analysis of RBM47 expression in human cancer patient data (lung, breast, gastric).
  • Investigated RBM47's interaction with KEAP1 and Cullin 3 mRNAs and its effect on Nrf2 activity.
  • Assessed RBM47's impact on mitochondrial respiration and cancer cell populations.
  • Evaluated RBM47's role in tumor formation and metastasis in xenograft mouse models.

Main Results:

  • TGF-β repressed RBM47 expression in epithelial and lung cancer cells.
  • RBM47 expression correlated with favorable prognosis in lung, breast, and gastric cancers.
  • RBM47 suppressed cell metabolism genes targeted by Nrf2.
  • RBM47 knockdown led to increased Nrf2 activity, enhanced Nrf2 activator expression, elevated mitochondrial respiration, and increased side population cells.
  • RBM47 knockdown promoted tumor formation and metastasis in vivo.

Conclusions:

  • RBM47 exhibits tumor-suppressive functions by inhibiting Nrf2 activity.
  • RBM47 plays a critical role in regulating cancer cell metabolism and progression.
  • RBM47 represents a potential therapeutic target for inhibiting cancer growth and metastasis.

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