Knockdown of Snail inhibits epithelial-mesenchymal transition of human laryngeal squamous cell carcinoma Hep-2 cells through the vitamin D receptor signaling pathway
Knockdown of Snail inhibits epithelial-mesenchymal transition of human laryngeal squamous cell carcinoma Hep-2 cells through the vitamin D receptor signaling pathway
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敲低Snail通过维生素D受体信号通路抑制人喉鳞状细胞癌Hep-2细胞的上皮间质转化
DOI：
10.1139/bcb-2017-0039
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发表时间：
2017
影响因子：
2.9
通讯作者：
Jin Chunshun
中科院分区：
文献类型：
--
作者：
Zhao Xue;Yu Dan;Yang Jingpu;Xue Kai;Liu Yan;Jin Chunshun
已有文献表明，蜗牛在多种肿瘤中起决定性作用。然而，Snail对喉鳞状细胞癌(LSCC)的直接作用尚未阐明。在本研究中，我们首先检测了14例喉鳞癌组织中Snail的表达，发现Snail在癌组织中的含量高于癌旁组织。建立了Snail沉默的喉癌Hep-2细胞，并通过Western blotting和Real-Time-PCR验证了基因敲除效率。结果表明，沉默蜗牛可显著抑制Hep-2细胞的黏附、迁移和侵袭能力。进一步研究发现，Snail基因敲除可抑制HEP-2细胞上皮-间充质转化过程，表现为基质金属肽酶-2、基质金属肽酶-9、整合素亚单位β1、β-连环蛋白、波形蛋白、N-钙粘蛋白和纤维连接蛋白表达下调，维生素D受体和E-钙粘蛋白表达上调。此外，转染VDR的小干扰RNA可逆转蜗牛沉默对Hep-2细胞的影响。综上所述，这些结果表明，Snail基因的敲除在体外可以通过VDR信号通路抑制LSCC细胞的EMT过程。
It has been well documented that Snail plays a decisive role in various tumors. However, the direct effect of Snail on laryngeal squamous cell carcinoma (LSCC) has not been elaborated. In this study, we firstly detected the expression of Snail in 14 samples of patients with LSCC and found that its content was high in cancer tissues compared with adjacent tissues. Then we established LSCC Hep-2 cells with Snail silencing and validated the knockdown efficiency by Western blotting and real-time PCR. Results showed that silencing of Snail significantly inhibited the ability of adhesion, migration, and invasion of Hep-2 cells. Further study revealed that knockdown of Snail suppressed the epithelial–mesenchymal transition (EMT) process of Hep-2 cells, as evidenced by downregulation of matrix metallopeptidase (MMP)-2, MMP-9, integrin subunit beta 1 (ITGβ1), β-catenin, vimentin, N-cadherin, and fibronectin and upregulation of vitamin D receptor (VDR) and E-cadherin. Additionally, transfection with the small interfering RNA of VDR reversed the effect induced by Snail silencing in Hep-2 cells. Taken together, these results demonstrate that knockdown of Snail can inhibit the EMT process of LSCC cells through the VDR signaling pathway in vitro.