Abstract
BackgroundGeneral 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.ResultsIn 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 p21Cip1/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.ConclusionSince 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.
Highlights
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
GCN5 expression is frequently up‐regulated in human Hepatocellular carcinoma (HCC) tissues and cell lines To evaluate the involvement of GCN5 in HCC, we examined the expression of GCN5 in a set of 31 human HCC specimens and four different human HCC cell lines by Western blot analysis
Our results showed that GCN5 protein levels were significantly up-regulated in 17 specimens (54.8 %), but down-regulated in 8 specimens (25.8 %), in total of 31 HCC specimens versus the surrounding non-tumorous liver tissues (Fig. 1a)
Summary
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. GCN5 has recently been implicated in certain oncogenic roles, its role in liver cancer progression remains vague. General control non-depressible 5 (GCN5), is the first identified transcription-related histone acetyl transferase (HAT), and a vital catalytic component of a transcriptional regulatory complex. GCN5 plays an important role in cellular functions, from cell cycle regulation to DNA damage repair [4,5,6]. GCN5 has been implicated in certain oncogenic roles. GCN5 increases the stability of c-Myc protein by acetylating its K323 residue [8, 9].
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