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Cell Biosci. 2016 Aug 2;6:47. doi: 10.1186/s13578-016-0114-6. eCollection 2016.

Histone acetyl transferase GCN5 promotes human hepatocellular carcinoma progression by enhancing AIB1 expression.

Majaz S#1, Tong Z#1, Peng K1, Wang W1, Ren W1, Li M2, Liu K1,3, Mo P1, Li W2, Yu C1,2,4.

Author information

1
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, 361102 Fujian China.
2
Xiamen City Key Laboratory of Biliary Tract Diseases, Chenggong Hospital of Xiamen University, Xiamen, China.
3
Department of Pathology, Chenggong Hospital of Xiamen University, Xiamen, China.
4
School of Life Sciences, Engineering Research Center of Molecular Diagnostics, Ministry of Education, Xiamen University, Xiamen, China.
#
Contributed equally

Abstract

BACKGROUND:

General control non-depressible 5 (GCN5) is a crucial catalytic component of a transcriptional regulatory complex that plays important roles in cellular functions from cell cycle regulation to DNA damage repair. Although GCN5 has recently been implicated in certain oncogenic roles, its role in liver cancer progression remains vague.

RESULTS:

In this study, we report that GCN5 was overexpressed in 17 (54.8 %) of 31 human hepatocellular carcinoma (HCC) specimens. Down-regulation of GCN5 inhibited HCC cell proliferation and xenograft tumor formation. GCN5 knockdown decreased the protein levels of the proliferation marker proliferating cell nuclear antigen (PCNA) and amplified in breast cancer 1 (AIB1), but increased the protein levels of cell cycle inhibitor p21(Cip1/Waf1) in HepG2 cells. GCN5 regulated AIB1 expression, at least in part, by cooperating with E2F1 to enhance AIB1 transcription. Consistently, GCN5 expression was positively correlated with AIB1 expression in human HCC specimens in two GEO profile datasets.

CONCLUSION:

Since AIB1 plays a promoting role in HCC progression, our results propose that GCN5 promotes HCC progression at least partially by regulating AIB1 expression. This study implicates that GCN5 might be a potential molecular target for HCC diagnosis and treatment.

KEYWORDS:

Amplified in breast cancer 1 (AIB1); Cell proliferation; General control non-depressible 5 (GCN5); Hepatocellular carcinoma (HCC); Histone acetyl transferase (HAT)

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