ARG1在肝细胞癌进展和转移中的致癌作用。,BioMed Research International

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ARG1在肝细胞癌进展和转移中的致癌作用。
BioMed Research International ( IF 2.6 ) Pub Date : 2018-09-18 , DOI: 10.1155/2018/2109865
Jia You ₁ , Wei Chen ₁ , Jing Chen ₁ , Qi Zheng ₁ , Jing Dong ₁ , Yueyong Zhu ₁

Affiliation

编码Arginase1的ARG1在肝细胞质中表达，在肝尿素循环中起主要作用。过去的研究揭示了ARG1参与抗发炎，肿瘤免疫和免疫抑制相关疾病的事实。然而，ARG1在肝细胞癌（HCC）进展中的具体作用和临床意义仍不清楚。在本文中，我们旨在检查ARG1在肝癌中的表达和临床病理学意义，以及确定ARG1对肝癌进展和转移的影响。在当前的研究中，在人类HCC组织微阵列中评估了ARG1的表达和ARG1的临床病理学意义，并构建了ARG1过表达载体和shRNA-ARG1质粒，以评估ARG1对Huh7细胞行为的具体影响。正如我们的数据揭示的那样，ARG1在肝癌中显着下调，而ARG1的高表达与更具侵略性的肿瘤生长，大小，ALT和GGT水平呈正相关。重要的是，我们发现ARG1的高表达与肝癌患者DFS差有关。此外，体外研究表明ARG1的过表达可以增强Huh7细胞的精氨酸酶活性，细胞活力，迁移和侵袭，而shRNA干扰导致ARG1的功能丧失可以抑制这些细胞的行为。此外，ARG1的过度表达导致波形蛋白，N-钙黏着蛋白和正如我们的数据揭示的那样，ARG1在肝癌中显着下调，而ARG1的高表达与更具侵略性的肿瘤生长，大小，ALT和GGT水平呈正相关。重要的是，我们发现ARG1的高表达与肝癌患者DFS差有关。此外，体外研究表明ARG1的过表达可以增强Huh7细胞的精氨酸酶活性，细胞活力，迁移和侵袭，而shRNA干扰导致ARG1的功能丧失可以抑制这些细胞的行为。此外，ARG1的过度表达导致波形蛋白，N-钙黏着蛋白和正如我们的数据揭示的那样，ARG1在肝癌中显着下调，而ARG1的高表达与更具侵略性的肿瘤生长，大小，ALT和GGT水平呈正相关。重要的是，我们发现ARG1的高表达与肝癌患者DFS差有关。此外，体外研究表明ARG1的过表达可以增强Huh7细胞的精氨酸酶活性，细胞活力，迁移和侵袭，而shRNA干扰导致ARG1的功能丧失可以抑制这些细胞的行为。此外，ARG1的过度表达导致波形蛋白，N-钙黏着蛋白和我们发现ARG1的高表达与肝癌患者DFS差有关。此外，体外研究表明ARG1的过表达可以增强Huh7细胞的精氨酸酶活性，细胞活力，迁移和侵袭，而shRNA干扰导致ARG1的功能丧失可以抑制这些细胞的行为。此外，ARG1的过度表达导致波形蛋白，N-钙黏着蛋白和我们发现ARG1的高表达与肝癌患者DFS差有关。此外，体外研究表明ARG1的过表达可以增强Huh7细胞的精氨酸酶活性，细胞活力，迁移和侵袭，而shRNA干扰导致ARG1的功能丧失可以抑制这些细胞的行为。此外，ARG1的过度表达导致波形蛋白，N-钙黏着蛋白和β-连环蛋白在蛋白质和mRNA水平上均能促进EMT过程。另一方面，这些蛋白的表达在ARG1沉默的Huh7细胞中显着下调。此外，在被击倒的ARG1细胞中E-钙粘蛋白的水平也被上调。总之，ARG1作为癌基因可能通过促进EMT过程在肝癌的发展中起关键作用。

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The Oncogenic Role of ARG1 in Progression and Metastasis of Hepatocellular Carcinoma.

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.

更新日期：2018-09-18

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