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SOX9 is controlled by the BRD4 inhibitor JQ1 via multiple regulation mechanisms

Seong Hwi Hong1, Jueng Soo You2

  • 1Department of Biochemistry, School of Medicine, Konkuk University, Seoul, 05029, South Korea.

Biochemical and Biophysical Research Communications
|March 6, 2019
PubMed

Insights

The bromodomain inhibitor JQ1 downregulates SOX9, a key factor in cell differentiation and cancer. This suggests targeting BRD4 offers a new therapeutic strategy for SOX9-driven diseases.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Research

Background:

  • SOX9 is a crucial transcription factor involved in cell differentiation, sex determination, and cancer development.
  • The precise mechanisms governing SOX9's targeting strategy and its therapeutic potential remain unclear.
  • Certain human cancers exhibit high SOX9 expression, with its downregulation showing anti-tumorigenic effects.

Purpose of the Study:

  • To explore the potential of targeting SOX9 using epigenetic drugs.
  • To elucidate the detailed molecular mechanisms underlying SOX9 regulation by epigenetic modulators.
  • To investigate the therapeutic implications of targeting SOX9 in cancer.

Main Methods:

  • Utilized two human cancer cell lines with high SOX9 expression as model systems.
  • Conducted histone acetylation-related screening of epigenetic drugs.
  • Investigated the effects of the bromodomain reader inhibitor JQ1 on SOX9 expression and function.

Main Results:

  • JQ1 significantly downregulated SOX9 expression through multiple regulatory steps.
  • JQ1 affected SOX9 at the transcriptional level.
  • JQ1 disrupted BRD4-SOX9 protein-protein interactions and reduced SOX9 protein stability.

Conclusions:

  • BRD4 inhibition represents a novel therapeutic strategy for diseases characterized by SOX9 overexpression.
  • Targeting the interaction between BRD4 and SOX9 can modulate SOX9 activity.
  • Epigenetic drugs like JQ1 offer promising avenues for cancer therapy by targeting key transcription factors.
Keywords:
BRD4Epigenetic drugJQ1Lysine acetylationSOX9

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