转录因子Snail介导E-cadherin表达在食管鳞癌迁移和侵袭中的作用

doi:10.3969/j.issn.1005-6483.2019.07.007

摘要/Abstract

摘要： 目的：探索转录因子Snail、Ecadherin基因在食管鳞癌中的表达及临床病理意义，明确其对食管鳞癌迁移和侵袭的影响。方法：食管鳞癌组织及对应癌旁组织标本30例，PCR检测Snail、Ecadherin表达；以癌/癌旁组织相对表达量表示Snail及Ecadherin在mRNA水平表达的差异，分析其与临床病理特征间关系；随机抽取其中4例，Western blot检测Snail、Ecadherin表达。筛选三株食管鳞癌细胞株中的一株进行转染，利用Snail小干扰RNA作为实验组，以双链无义RNA转染作为对照组，检测Snail和Ecadherin表达水平变化，行细胞划痕、侵袭实验。结果：30例食管鳞癌组织较癌旁组织中Snail相对表达量高（1.96±0.75/0.52±0.43，P=0.04），Ecadherin相对表达量低（0.66±0.31/2.19±0.62，P=0.02）；食管鳞癌中Snail相对高表达、Ecadherin相对低表达程度均与癌组织浸润深度（P=0.009）、淋巴结转移与否（P=0.047）相关。其中4例病人，癌组织相比对应癌旁组织中Snail蛋白表达高（0.73±0.13/0.23±0.08，P=0.00），而Ecadherin蛋白表达低（0.10±0.06/0.60±0.14，P=0.00）。选取EC109为实验细胞株，PCR结果显示，Snail小干扰RNA转染组较对照组中Snail表达减少（0.53±0.05/1.00±0.15，P=0.00），同时，Ecadherin表达上调（3.28±0.26/1.00±0.18，P=0.00）；Western blot检测显示，抑制Snail蛋白表达后（0.25±0.05/0.41±0.10，P=0.03）EC109中Ecadherin蛋白表达上调（0.83±0.11/0.29±0.05，P=0.02）。划痕实验及Transwell细胞侵袭实验示，下调Snail表达后EC109迁移、侵袭能力均减弱（P<0.05）。结论：转录因子Snail在食管鳞癌中相对高表达，并可能通过介导Ecadherin表达影响肿瘤迁移与侵袭。

关键词: 食管鳞癌, Snail, E-cadherin, 迁移, 侵袭

Abstract: Objective：To determine the expression of Snail and Ecadherin in esophageal squamous cell carcinoma （ESCC）.To detect the effect of Snail on influencing the migration and invasion of ESCC by targeting Ecadherin.Methods：The expression of Snail and Ecadherin were detected in 30 clinical ESCC samples and its adjacent normal epithelial samples via Polymerase Chain Reaction （PCR）.The relative expression of Snail and Ecadherin in ESCC and its adjacent normal tissue were analysed with these 30 patients’ clinical pathological characteristics .The expression of Snail and Ecadherin in 4 random pairs of these 30 samples were investigated via Western Blot.Based on cell transfection of one ESCC cell line，the expression of Snail was downregulated with the Snail small interfering RNA （siRNA）.Then the expression of Snail and Ecadherin expression in these models were analyzed and the cell wound healing assay and invasion functional experiment were carried out.Result：The relative expression of 30 cases of esophageal squamous cell carcinoma was higher than that of the adjacent tissues of Snail（1.96±0.75/0.52±0.43，P=0.04），the relative expression of Ecadherin was low（0.66±0.31/2.19±0.62，P=0.02）.Depth of tumor invasion （P=0.009）and tumor metastasis to lymph nodes （P=0.047）were associated with overexpression of Snail and lowexpression of Ecadherin .In 4 random matched samples，the expression of Snail was 0.73±0.13 in cancer samples and 0.23±0.08 in its adjacent samples，meanwhile the expression of Ecadherin was 0.10±0.06 in tumor tissues and 0.60±0.14 in normal tissues（P=0.00）.The cell line EC109 was selected into the transfection model.Compared with negative control group，depression of Snail（0.53±0.05/1.00±0.15，P=0.00）could restore the expression of Ecadherin （3.28±0.26/1.00±0.18，P=0.00）in mRNA level，as well as in the level of protein（0.25±0.05/0.41±0.10，P=0.03；0.83±0.11/0.29±0.05，P=0.02）.Downregulated the expression of Snail also decreased the capability of migration and invasion in EC109（P<0.05）.Conclusion：Relatively high expression of Snail in ESCC may influence the migration and invasion in ESCC by regulating Ecadheirn.

Key words: esophageal squamous cell carcinoma, Snail, E-cadherin, migration, invasion

王江陵, 魏远福, 江海. 转录因子Snail介导E-cadherin表达在食管鳞癌迁移和侵袭中的作用[J]. 临床外科杂志, 2019, 27(7): 562-565.

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