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Updated: Jun 28, 2025

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HDAC10 inhibition represses melanoma cell growth and BRAF inhibitor resistance via upregulating SPARC expression

Hongbo Ling1, Yixuan Li1, Changmin Peng1

  • 1George Washington Cancer Center, Department of Biochemistry & Molecular Medicine, The George Washington University School of Medicine & Health Sciences, Washington, DC 20037, USA.

NAR Cancer
|April 23, 2024
PubMed

Insights

Histone deacetylase 10 (HDAC10) regulates SPARC expression in melanoma. Inhibiting HDAC10 increases SPARC, repressing cancer cell growth and resensitizing resistant cells to BRAF inhibitors.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • Secreted protein acidic and rich in cysteine (SPARC) is a glycoprotein involved in biological processes.
  • SPARC is highly expressed in melanoma, impacting cancer progression.
  • Understanding SPARC regulation is key for improved cancer therapies.

Purpose of the Study:

  • To identify key regulators of SPARC expression in melanoma.
  • To elucidate the molecular mechanisms controlling SPARC transcription.
  • To explore the therapeutic potential of targeting SPARC regulation in melanoma.

Main Methods:

  • Depletion and overexpression of histone deacetylase 10 (HDAC10) in melanoma cells.
  • Chromatin immunoprecipitation (ChIP) assays to assess histone modifications and protein recruitment.
  • Analysis of cell growth, AMPK signaling, autophagy, and drug sensitivity.

Main Results:

  • HDAC10 depletion or inhibition upregulates SPARC expression; HDAC10 overexpression downregulates it.
  • HDAC10 modulates SPARC transcription via H3K27ac and BRD4 recruitment at regulatory elements.
  • SPARC upregulation induced by HDAC10 depletion inhibits melanoma cell growth by activating AMPK and autophagy.
  • HDAC10 inhibition resensitizes resistant melanoma cells to BRAF inhibitors.

Conclusions:

  • HDAC10 is a critical regulator of SPARC expression in melanoma.
  • Targeting HDAC10 offers a potential therapeutic strategy for melanoma by modulating SPARC.
  • This study reveals a novel mechanism of gene regulation through indirect histone modification.

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