4.7 Article

Histone acetyltransferase PCAF Up-regulated cell apoptosis in hepatocellular carcinoma via acetylating histone H4 and inactivating AKT signaling

Journal

MOLECULAR CANCER
Volume 12, Issue -, Pages -

Publisher

BIOMED CENTRAL LTD
DOI: 10.1186/1476-4598-12-96

Keywords

PCAF; Hepatocellular carcinoma; AKT signaling; Histone H4; Apoptosis

Funding

  1. National Natural Scientific Foundation of China [81272645, 81072052, 81071897]
  2. Research Fund for the doctoral Program of High Education of China from Ministry of Education [20120201120090]
  3. Fundamental Research Funds for the Basic Research Operating expenses Program of Central College
  4. Xi'an Jiaotong University

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Background: PCAF is an important intrinsic histone acetyltransferases. This study tried to establish the effect of PCAF on HCC cell apoptosis. Method: Both in vitro and in vivo experiments including IHC, DAPI staining, caspase 3/7 activity assay, BrdU assay, MTT assay, western immunoblotting and co-immunoprecipitation were used here. Results: PCAF was found to be expressed at the low level in most of HCC cell lines. PCAF overexpression induced cell apoptosis and growth arrest with increased Histone H4 acetylation and inactivation of AKT signaling in Huh7 and HepG2 cells. The opposite results were obtained by silencing PCAF in Hep3B cells. The co-immunoprecipitation assay confirmed that PCAF protein was bound with histone H4 protein in the nucleus of Hep3B cells. Finally, the in vivo experiment confirmed the findings mentioned-above. Conclusion: These data identified PCAF promotes cell apoptosis and functions as a HCC repressor through acetylating histone H4 and inactivating AKT signaling.

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