Histone acetyl transferase GCN5 promotes human hepatocellular carcinoma progression by enhancing AIB1 expression.
Histone acetyl transferase GCN5 promotes human hepatocellular carcinoma progression by enhancing AIB1 expression.
复制标题
组蛋白乙酰转移酶 GCN5 通过增强 AIB1 表达促进人肝细胞癌进展。
DOI：
10.1186/s13578-016-0114-6
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发表时间：
2016
影响因子：
7.5
通讯作者：
Yu C
中科院分区：
文献类型：
--
作者：
Majaz S;Tong Z;Peng K;Wang W;Ren W;Li M;Liu K;Mo P;Li W;Yu C
GCN 5是转录调控复合物的关键催化组分，在从细胞周期调控到DNA损伤修复的细胞功能中发挥重要作用。虽然GCN 5最近被认为与某些致癌作用有关，但其在肝癌进展中的作用仍然模糊。在这项研究中，我们报告了GCN 5在31例人肝细胞癌（HCC）标本中的17例（54.8%）过表达。下调GCN 5可抑制HCC细胞增殖和异种移植瘤形成。GCN 5基因敲低降低了增殖标记物增殖细胞核抗原（PCNA）的蛋白水平，并在乳腺癌1（AIB 1）中扩增，但增加了HepG 2细胞中细胞周期抑制因子p21 Cip 1/Waf 1的蛋白水平。GCN 5调控AIB 1的表达，至少部分是通过与E2 F1协同作用来增强AIB 1的转录。一致地，在两个GEO图谱数据集中，人HCC标本中GCN 5表达与AIB 1表达正相关。由于AIB 1在HCC进展中起促进作用，我们的研究结果表明GCN 5至少部分通过调节AIB 1表达来促进HCC进展。GCN 5可能成为肝癌诊断和治疗的潜在分子靶点。
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. 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 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. 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.