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

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.