EZH2 regulates expression of FOXC1 by mediating H3K27me3 in breast cancers

Xiang-Jin Zheng1,2, Wan Li1,2, Jie Yi3

  • 1The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing, 100050, China.

Insights

FOXC1 is highly expressed in triple-negative breast cancer (TNBC) and linked to poor survival and doxorubicin resistance. Targeting FOXC1 may offer new therapeutic strategies for TNBC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype lacking specific biomarkers and effective treatments.
  • Understanding TNBC's underlying mechanisms is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of FOXC1 in TNBC.
  • To identify potential biomarkers and therapeutic targets for TNBC.

Main Methods:

  • In silico analysis, qRT-PCR, immunohistochemistry, and Western blot were used to assess FOXC1 expression.
  • Kaplan-Meier plotter analyzed the association between FOXC1 expression and patient survival.
  • Cell-based assays examined the relationship between FOXC1, EZH2, H3K27me3, and doxorubicin resistance.

Main Results:

  • FOXC1 was significantly upregulated in TNBC compared to other breast cancer subtypes.
  • High FOXC1 expression correlated with poorer overall survival in breast cancer patients.
  • FOXC1 expression was inversely associated with H3K27me3 levels, modulated by EZH2.
  • FOXC1 expression was linked to doxorubicin resistance in breast cancer cells.

Conclusions:

  • FOXC1 may serve as a potential biomarker for TNBC.
  • Targeting FOXC1, possibly by downregulating its expression, could be a therapeutic strategy for TNBC.
  • Further research into FOXC1's role could lead to novel treatments for this aggressive cancer subtype.

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