Histone deacetylase 3 participates in self-renewal of liver cancer stem cells through histone modification

Cancer Lett. 2013 Oct 1;339(1):60-9. doi: 10.1016/j.canlet.2013.07.022. Epub 2013 Jul 20.


Understanding molecular mechanisms in self-renewal of cancer stem cells (CSCs) is important for finding novel target in therapy of cancer. In this study, we explored potential effects of histone deacetylase (HDAC) on liver CSCs. Our data showed that HDAC inhibitors suppressed self-renewal and induced differentiation of liver CSCs. Furthermore, we demonstrated that HDAC3 was selectively expressed in liver CSCs and participated in self-renewal of liver CSCs via regulating expression of pluripotency factors. Overexpression of HDAC3 was associated with poor outcome of liver cancer. HDAC inhibitors could render liver CSCs sensitive to sorafenib. Taken together, our data suggest that HDAC3 plays a critical role in regulating self-renewal of liver CSCs.

Keywords: Cancer stem cells; HCC; HDAC3; Histone modification; Self-renewal; TSA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression
  • Gene Knockdown Techniques
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Histones / metabolism*
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / mortality
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Niacinamide / analogs & derivatives
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / therapeutic use
  • Prognosis
  • Sorafenib


  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • Histones
  • Phenylurea Compounds
  • Niacinamide
  • Sorafenib
  • Histone Deacetylases
  • histone deacetylase 3