Zhao Xue, Yu Dan, Yang Jingpu, Xue Kai, Liu Yan, Jin Chunshun
Department of Otolaryngology, Head and Neck Surgery, The Second Hospital of Jilin University, Changchun 130041, People's Republic of China.
Biochem Cell Biol. 2017 Dec;95(6):672-678. doi: 10.1139/bcb-2017-0039. Epub 2017 Aug 14.
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.
已有充分文献证明，Snail在各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LSCC患者样本中Snail的表达，发现与癌旁组织相比，其在癌组织中的含量较高。然后我们建立了Snail沉默的LSCC Hep-2细胞，并通过蛋白质免疫印迹法和实时荧光定量PCR验证了敲低效率。结果表明，Snail沉默显著抑制了Hep-2细胞的黏附、迁移和侵袭能力。进一步研究表明，Snail敲低抑制了Hep-2细胞的上皮-间质转化（EMT）过程，表现为基质金属蛋白酶（MMP）-2、MMP-9、整合素亚基β1（ITGβ1）、β-连环蛋白、波形蛋白、N-钙黏蛋白和纤连蛋白的下调以及维生素D受体（VDR）和E-钙黏蛋白的上调。此外，用VDR的小干扰RNA转染可逆转Snail沉默在Hep-2细胞中诱导的效应。综上所述，这些结果表明，在体外，Snail敲低可通过VDR信号通路抑制LSCC细胞的EMT过程。
