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Methods to Discover Alternative Promoter Usage and Transcriptional Regulation of Murine Bcrp1
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Methods to Discover Alternative Promoter Usage and Transcriptional Regulation of Murine Bcrp1

Published on: May 27, 2016

RBM5 Acts as a Tumor Suppressor in Breast Cancer Through Binding to G-quadruplexes in the BAP1 Gene Promoter to

Yingzhou Li1, Wenmeng Wang1, Guangyue Li2

  • 1College of Life Science, Northeast Forestry University, Harbin 150040, China.

Molecules (Basel, Switzerland)
|July 28, 2026
PubMed

Insights

RNA-binding motif protein 5 (RBM5) suppresses breast cancer by stabilizing the BAP1 promoter G-quadruplex. This interaction transcriptionally activates BAP1, reducing cancer cell malignancy and tumor growth.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • RNA-binding motif protein 5 (RBM5) is a known tumor suppressor in lung and prostate cancers.
  • RBM5 regulates alternative splicing of apoptosis and cell cycle genes.
  • RBM5's role in direct gene transcription regulation was previously unreported.

Purpose of the Study:

  • To investigate the role of RBM5 in breast cancer.
  • To determine if RBM5 directly regulates gene transcription.
  • To elucidate the mechanism by which RBM5 functions as a tumor suppressor in breast cancer.

Main Methods:

  • Analysis of RBM5 expression in breast cancer cell lines and clinical samples.
  • Assessment of RBM5's effect on breast cancer cell malignancy in vitro and tumor growth in vivo.
  • Investigation of RBM5 binding to G-quadruplex (G4) motifs in gene promoters (MYC, BAP1).
  • Evaluation of RBM5's impact on G4 structure stability and gene expression.
  • Functional rescue experiments using BAP1 overexpression.

Main Results:

  • RBM5 is significantly downregulated in breast cancer, particularly in the basal-like subtype.
  • RBM5 overexpression inhibits breast cancer cell malignancy; knockdown promotes it.
  • RBM5 binds to G4 motifs in MYC and BAP1 promoters, destabilizing MYC-G4 and stabilizing BAP1-G4.
  • RBM5 specifically upregulates BAP1 expression by stabilizing its promoter G4.
  • BAP1 overexpression reverses the protumorigenic effects of RBM5 knockdown.

Conclusions:

  • RBM5 functions as a tumor suppressor in breast cancer.
  • RBM5 directly activates BAP1 transcription by stabilizing its promoter G4 structure.
  • RBM5 represents a potential therapeutic target for breast cancer treatment.
Keywords:
BAP1G-quadruplexRBM5breast cancertumor suppressor

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