Mediator subunit 23 overexpression as a novel target for suppressing proliferation and tumorigenesis in hepatocellular carcinoma
Mediator subunit 23 overexpression as a novel target for suppressing proliferation and tumorigenesis in hepatocellular carcinoma
复制标题
介导亚基 23 过表达作为抑制肝细胞癌增殖和肿瘤发生的新靶点。
DOI：
10.1111/jgh.12923
复制
发表时间：
2015-06-01
影响因子：
4.1
通讯作者：
Chen, Guihua
中科院分区：
文献类型：
--
作者：
Guo, Yu;Wang, Jing;Chen, Guihua
背景与目的肝细胞癌（Hepatocellular carcinoma，HCC）是世界上第五大常见的恶性肿瘤.然而，肝癌的分子机制仍然知之甚少。在这里，我们研究的调解子亚基23（MED 23），一个组成部分的调解人复杂的，在hepatocarcinogenes.MethodsWe检测MED 23的表达在肝癌标本的实时聚合酶链反应（PCR）和免疫组化分析的作用。我们还敲低并过表达MED 23，以探索其在肝癌细胞生长中的功能作用。流式细胞仪检测细胞周期，Western blot检测蛋白表达。采用小鼠异种移植瘤模型检测MED 23是否参与肝癌的发生。结果MED 23在人肝癌组织中的表达明显高于癌旁正常肝组织。肝癌细胞也显示出增加的MED 23表达。MED 23敲低抑制肝癌细胞生长，而MED 23过表达促进细胞生长。MED 23的敲低诱导G1至S期阻滞。此外，MED 23调节p16（INK 4a）（p16）的表达和视网膜母细胞瘤蛋白（Rb）的磷酸化。p16转录上调，其启动子脱甲基化。p16基因沉默后，MED 23基因敲除诱导的G1期至S期阻滞中止。此外，MED 23基因敲低可抑制肝癌的发生，并调节p16/Rb信号通路。结论MED 23基因在肝癌发生中起重要作用，可能成为肝癌治疗的新靶点。
Background and AimHepatocellular carcinoma (HCC) is the fifth most frequent cancer in the world. However, the molecular mechanisms involved in HCC are still poorly understood. Here, we study the role of mediator subunit 23 (MED23), a component of the Mediator complex, in hepatocarcinogenesis.MethodsWe detected MED23 expression in HCC samples by real-time polymerase chain reaction (PCR) and immunohistochemistry analysis. We also knocked down and overexpressed MED23 to explore its functional role in hepatoma cell growth. The cell cycle was examined by flow cytometry analysis, and protein expression was examined by Western blot. A xenograft mouse model was used to determine whether MED23 is involved in tumorigenesis.ResultsMED23 was frequently upregulated in human HCC tissues compared with paired adjacent non-tumorous liver tissues. The hepatoma cells also showed increased MED23 expression. MED23 knockdown inhibited hepatoma cell growth, whereas overexpression of MED23 promoted cell growth. Knockdown of MED23 induced a G1 to S phase arrest. Moreover, MED23 regulated the expression of p16(INK4a) (p16) and the phosphorylation of retinoblastoma protein (Rb). p16 was transcriptionally upregulated, and its promoter was demethylated. The G1 to S phase arrest induced by MED23 knockdown was aborted after p16 was silenced. Furthermore, MED23 knockdown suppressed tumorigenesis and regulated p16/Rb signaling in vivo.ConclusionsTaken together, our study suggests that MED23 plays an important role in hepatocarcinogenesis, and it may be a novel target for HCC therapy.