A20 suppresses hepatocellular carcinoma proliferation and metastasis through inhibition of Twist1 expression.
A20 suppresses hepatocellular carcinoma proliferation and metastasis through inhibition of Twist1 expression.
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A20通过抑制Twist1表达抑制肝细胞癌增殖和转移
DOI：
10.1186/s12943-015-0454-6
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发表时间：
2015-11-04
期刊：
影响因子：
37.3
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Chen H;Hu L;Luo Z;Zhang J;Zhang C;Qiu B;Dong L;Tan Y;Ding J;Tang S;Shen F;Li Z;Wang H
据报道，A20在包括肝细胞癌（HCC）在内的多种人类恶性肿瘤中表达异常。然而，其在肝细胞癌中的临床相关性及潜在作用仍不明确。
采用定量PCR、蛋白质印迹和免疫组化分析来量化肝细胞癌样本及细胞系中A20的表达。在一个包含143例原发性肝细胞癌患者的队列中分析了A20表达与临床病理特征的相关性。利用卡普兰 - 迈耶曲线评估A20表达与患者生存率之间的关联。进行功能研究以确定A20在体外和体内对肝细胞癌细胞增殖和转移的影响。
A20在肝细胞癌组织和细胞系中的表达增加。A20表达增加与肿瘤大小、TNM分期、肿瘤血栓形成、包膜侵犯以及血清甲胎蛋白水平呈负相关。A20表达较高的患者无病生存期和总生存期比A20表达较低的患者更长。A20的过表达在体外和体内均显著抑制肝细胞癌细胞的增殖和侵袭特性，而A20表达的敲低则显示出相反的效果。进一步研究表明，在肝细胞癌组织和细胞系中，A20的表达与Twist1水平和NF - κB活性呈负相关。A20对肝细胞癌细胞增殖和迁移的抑制作用主要是通过抑制Twist1表达来介导的，而Twist1表达至少部分是由A20诱导的NF - κB活性减弱所调控的。
我们的研究结果表明，A20可能通过抑制Twist1表达在肝细胞癌的发生和发展中起负向作用。A20可作为肝细胞癌患者一种新的预后生物标志物和潜在的治疗靶点。
本文的网络版（doi:10.1186/s12943 - 015 - 0454 - 6）包含补充材料，授权用户可获取。
BackgroundAberrant expression of A20 has been reported in several human malignancies including hepatocellular carcinoma (HCC). However, its clinical relevance and potential role in HCC remain unknown.MethodsQuantitative PCR, Western blots and immunohistochemistry analyses were used to quantify A20 expression in HCC samples and cell lines. The correlation of A20 expression with clinicopathologic features was analyzed in a cohort containing 143 patients with primary HCC. Kaplan-Meier curves were used to evaluate the association between A20 expression and patient survival. Functional studies were performed to determine the effects of A20 on proliferation and metastasis of HCC cells in vitro and in vivo.ResultsExpression of A20 was increased in HCC tissues and cell lines. Increased expression of A20 was negatively correlated with the tumor size, TNM stage, tumor thrombus formation, capsular invasion and serum AFP levels. Patients with higher A20 expression had a prolonged disease-free survival and overall survival than those with lower A20 expression. Forced expression of A20 significantly inhibited the proliferative and invasive properties of HCC cells both in vitro and in vivo, whereas knockdown of A20 expression showed the opposite effects. Further studies revealed that expression of A20 was inversely correlated with Twist1 levels and NF-κB activity in HCC tissues and cell lines. A20-induced suppression of proliferation and migration of HCC cells were mainly mediated through inhibition of Twist1 expression that was regulated at least partly by A20-induced attenuation of NF-κB activity.ConclusionsOur results demonstrate that A20 plays a negative role in the development and progression of HCC probably through inhibiting Twist1 expression. A20 may serve as a novel prognostic biomarker and potential therapeutic target for HCC patients.