The Oncogenic Role of ARG1 in Progression and Metastasis of Hepatocellular Carcinoma.
The Oncogenic Role of ARG1 in Progression and Metastasis of Hepatocellular Carcinoma.
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DOI：
10.1155/2018/2109865
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发表时间：
2018
影响因子：
--
通讯作者：
Zhu Y
中科院分区：
文献类型：
--
作者：
You J;Chen W;Chen J;Zheng Q;Dong J;Zhu Y
ARG 1编码精氨酸酶1，在肝细胞质中表达，在肝尿素循环中起主要作用。过去的研究工作揭示了ARG 1参与抗炎，肿瘤免疫和免疫抑制相关疾病的事实。然而，ARG 1在肝细胞癌（HCC）进展中的具体作用和临床意义仍不清楚。本研究旨在探讨ARG 1在肝癌组织中的表达及其临床病理意义，以及ARG 1在肝癌发生、发展和转移中的作用。本研究在人肝癌组织芯片中检测ARG 1的表达及其临床病理学意义，并构建ARG 1过表达载体和shRNA-ARG 1质粒，研究ARG 1对Huh 7细胞行为的具体影响。正如我们的数据显示，ARG 1在HCC中显著下调，ARG 1的高表达与更具侵袭性的肿瘤生长、大小、ALT和GGT水平呈正相关。值得注意的是，我们发现ARG 1的高表达与HCC患者的DFS差相关。此外，体外研究发现ARG 1过表达可增强Huh 7细胞的端粒酶活性、细胞活力、迁移和侵袭能力，而ARG 1功能缺失可抑制这些细胞行为。此外，ARG 1的过表达导致波形蛋白、N-钙粘蛋白和β-连环蛋白在蛋白质和mRNA水平上的表达显著增加，这促进了EMT过程。另一方面，这些蛋白质的表达在ARG 1沉默的Huh 7细胞中显著下调。此外，在ARG 1敲低的细胞中，E-cadherin蛋白水平上调。总之，ARG 1可能作为癌基因通过促进EMT过程在HCC的进展中发挥关键作用。
ARG1, which encodes Arginase1, is expressed in the liver cytoplasm and plays a major role in the hepatic urea cycle. The past research works shed light on the fact that ARG1 participates in anti-inflammation, tumor immunity, and immunosuppression-related diseases. Nevertheless, the concrete role and clinical significance of ARG1 in the progression of hepatocellular carcinoma (HCC) remain unclear. Herein, we aimed at examining the expression and clinicopathological significance of ARG1 in HCC, together with determining the effect of ARG1 on the progression and metastasis of HCC. In the current study, evaluation of the expression of ARG1 and clinicopathological significance of ARG1 was carried out in the human HCC tissues microarray, and the ARG1 overexpression vector and shRNA-ARG1 plasmids were constructed for the assessment of the concrete effect of ARG1 on cellular behaviors of Huh7 cells. As our data revealed, ARG1 was significantly downregulated in HCC, and the higher expression of ARG1 was positively correlated with more aggressive tumor growth, size, ALT, and GGT level. Significantly, we found that the high expression of ARG1 was correlated with poor DFS of HCC patients. Besides, in vitro study revealed that overexpression of ARG1 could enhance arginase activity, cell viability, migration, and invasion of Huh7 cells, and loss-of-function of ARG1 by shRNA interference could inhibit these cellular behaviors. Additionally, overexpression of ARG1 led to a significant increase in the expression of Vimentin, N-cadherin, and β-catenin both at protein and mRNA levels, which promotes the EMT process. On the other hand, these proteins' expression was significantly downregulated in ARG1 silenced Huh7 cells. Besides, the level of E-cadherin protein was upregulated in ARG1 knocked down cells. In conclusion, ARG1 might play a pivotal role as an oncogene in the progression of HCC through promoting the EMT process.
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影响因子：
29
作者：
Ochocki JD;Khare S;Hess M;Ackerman D;Qiu B;Daisak JI;Worth AJ;Lin N;Lee P;Xie H;Li B;Wubbenhorst B;Maguire TG;Nathanson KL;Alwine JC;Blair IA;Nissim I;Keith B;Simon MC
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