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Bromodomain Proteins Epigenetically Regulate the Mitotically Associated lncRNA MANCR in Triple Negative Breast Cancer

Kirsten M Tracy1, Shannon Prior2, Willem T Trowbridge1

  • 1Department of Biochemistry, University of Vermont Larner College of Medicine, Burlington, VT 05405.

Critical Reviews in Eukaryotic Gene Expression
|December 11, 2023
PubMed

Insights

Long non-coding RNA MANCR is crucial for triple-negative breast cancer (TNBC) cell survival and genome stability. Bromodomain proteins, particularly BRD4, regulate MANCR expression through epigenetic control of super enhancers.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Long non-coding RNAs (lncRNAs) regulate gene expression, impacting biological processes like cell proliferation and cancer progression.
  • lncRNAs are emerging as significant targets and biomarkers in breast cancer research.
  • The lncRNA MANCR is expressed in triple-negative breast cancer (TNBC) and is vital for aggressive cell survival and genome stability.

Purpose of the Study:

  • To investigate the role of bromodomain proteins (BRD2, BRD3, BRD4) in regulating the expression of lncRNA MANCR in TNBC cells.
  • To elucidate the epigenetic mechanisms underlying MANCR's function in TNBC.

Main Methods:

  • Small interfering RNA (siRNA) was used to deplete BRD2, BRD3, and BRD4 in TNBC cells.
  • In situ hybridization combined with immunofluorescence analysis was performed to confirm findings.
  • Epigenetic analysis focused on histone modifications and super enhancer activity.

Main Results:

  • BRD4, individually or with BRD2 and BRD3, was identified as a key regulator of MANCR expression in TNBC cells.
  • Evidence suggests MANCR-responsive epigenetic control of super enhancers via histone modifications.
  • These modifications are essential for gene transcription supporting TNBC cell survival and the epithelial tumor phenotype.

Conclusions:

  • Bromodomain proteins, especially BRD4, play a critical role in regulating MANCR expression in triple-negative breast cancer.
  • Epigenetic modifications of super enhancers, mediated by MANCR, are crucial for TNBC cell survival and progression.
  • MANCR represents a potential therapeutic target and biomarker for aggressive breast cancers.

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