Transcription factor RFX7 governs a tumor suppressor network in response to p53 and stress

Luis Coronel1, Konstantin Riege1, Katjana Schwab1

  • 1Computational Biology Group, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745 Jena, Germany.

Insights

The tumor suppressor p53 activates regulatory factor X 7 (RFX7), which controls other tumor suppressors. This p53-RFX7 pathway is crucial for cell growth, fate, and cancer prognosis.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Genetics

Background:

  • The tumor suppressor p53's gene regulation mechanisms are not fully understood.
  • Regulatory factor X 7 (RFX7) is a newly identified suppressor of lymphoid neoplasms, but its regulatory pathways and tumor-suppressive targets are unknown.

Purpose of the Study:

  • To elucidate the novel p53-RFX7 signaling axis.
  • To identify RFX7's direct target genes and their role in tumor suppression.

Main Methods:

  • Integrative analysis of RFX7 DNA binding landscape.
  • Transcriptome analysis in three distinct cell systems.
  • Correlation analysis of RFX7 target gene expression with cancer prognosis.

Main Results:

  • A novel p53-RFX7 signaling axis was identified.
  • RFX7 directly regulates established tumor suppressors (PDCD4, PIK3IP1, MXD4, PNRC1), acting as a link for their p53-mediated activation.
  • RFX7 target gene expression correlates with better cancer prognosis and cell differentiation.
  • RFX7 sensitizes cells to Doxorubicin by promoting apoptosis.

Conclusions:

  • RFX7 is a ubiquitous regulator of cell growth and fate determination.
  • RFX7 is a key component of the p53 transcriptional program, mediating tumor suppression through direct regulation of multiple target genes.

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