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Digestive Diseases and Sciences

, Volume 58, Issue 12, pp 3545–3553 | Cite as

The Up-Regulation of Histone Deacetylase 8 Promotes Proliferation and Inhibits Apoptosis in Hepatocellular Carcinoma

  • Jian Wu
  • Chengli Du
  • Zhen Lv
  • Chaofeng Ding
  • Jun Cheng
  • Haiyang Xie
  • Lin Zhou
  • Shusen Zheng
Original Article

Abstract

Background

Histone deacetylase 8 (HDAC8), a member of class I HDACs, has been reported to be involved in transcriptional regulation, cell cycle progression, and developmental events, and several studies have shown that HDAC8 plays a critical role in tumorigenesis. However, the expression level and the potential role of HDAC8 in hepatocellular carcinoma (HCC) remain unclear.

Aim

The purpose of this study was to investigate protein expression of HDAC8 in HCC tissues and the effects of HDAC8 knockdown on the proliferation and apoptosis of liver cancer cells, and to explore the possible mechanisms.

Methods

First, we used quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemical staining, and western blot to examine the mRNA and protein expression of HDAC8 in HCC cell lines and tissues. Then, we assessed the correlation between clinicopathological parameters and the protein expression of HDAC8. Furthermore, we employed the interfering RNA method to explore the potential role of HDAC8 in HCC progression in vitro.

Results

Our results showed that expression of HDAC8 was significantly up-regulated both in HCC cell lines and tumor tissues compared to human normal liver cell line LO2 and corresponding non-tumor tissues. Moreover, we found that HDAC8 knockdown could dramatically inhibit HCC cell proliferation and enhance the apoptosis rate in vitro. Western blot revealed that intrinsic apoptotic pathway proteins, including BAX, BAD, and BAK, were elevated after HDAC8 knockdown. The cleavage of caspase-3 and PARP, which are downstream of intrinsic apoptotic pathway, were also enhanced. In addition, suppression of HDAC8 also elevated the expression of p53 and acetylation of p53 at Lys382, whereas the acetylation of p53 at Lys373 did not change.

Conclusions

Our study revealed that HDAC8 was overexpressed in HCC. HDAC8 knockdown suppresses tumor growth and enhances apoptosis in HCC via elevating the expression of p53 and acetylation of p53 at Lys382. HDAC8 might serve as a potential therapeutic target in HCC.

Keywords

Hepatocellular carcinoma (HCC) HDAC8 Proliferation Apoptosis Intrinsic apoptotic pathways p53 Acetylation of p53 

Notes

Acknowledgments

This study was sponsored by Grants from the National Natural Science Foundation of China (No. 81272281) and Zhejiang Provincial Natural Science Foundation for Young Distinguished Scholars (No. R2110125).

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Jian Wu
    • 1
  • Chengli Du
    • 1
  • Zhen Lv
    • 1
  • Chaofeng Ding
    • 1
  • Jun Cheng
    • 1
  • Haiyang Xie
    • 1
  • Lin Zhou
    • 1
  • Shusen Zheng
    • 1
  1. 1.Department of Hepatobiliary Surgery, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina

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