FoxM1调控Snai1促进肝癌上皮-间充质转换的作用

THE ROLE OF FOXM1 AND SNAI1 IN THE EPITHELIAL-MESENCHYMAL TRANSITION OF HEPATOCELLULAR CARCINOMA

目的探讨肝细胞癌FoxM1的表达及其在上皮-间充质转换(EMT)中的作用及分子机制。方法采用Western blot和qRT-PCR方法,检测FoxM1、Snai1和E-cadherin在不同转移潜能的肝癌细胞系和正常肝细胞系中的表达水平。通过转染pcDNA3.1-FoxM1和siRNA-FoxM1调控FoxM1的表达,探讨FoxM1、Snai1在肝细胞癌EMT中的作用。采用划痕实验和Transwell实验检测FoxM1对肝癌细胞侵袭和迁移能力的作用。结果FoxM1在肝癌细胞中高表达(F=29.617、18.037,P<0.05),肝癌细胞中高表达的FoxM1与E-cadherin表达呈负相关(r=-0.893,P<0.05),与Snai1表达呈正相关(r=0.993,P<0.05)。划痕实验显示,下调FoxM1表达可以降低肝癌细胞的迁移能力(t=4.594,P<0.05),而上调FoxM1表达可以增加肝癌细胞的迁移能力(t=-4.459,P<0.05)。Transwell侵袭实验显示,下调FoxM1表达可以降低肝癌细胞的侵袭能力(t=-4.385,P<0.05),而上调FoxM1表达可以增加肝癌细胞的侵袭能力(t=-4.950,P<0.05)。结论 FoxM1在肝癌细胞中高表达,通过调控EMT促进肝癌细胞的迁移和侵袭,FoxM1可能成为肝癌治疗的新靶点。

Objective To investigate the expression of FoxM1 and its role as well as molecular mechanism in the epithelial-mesenchymal transition （EMT） of hepatoeellular carcinoma （HCC）. Methods Using the Western blot and qRT-PCR me- thods, the expressions of FoxM1, Snail and E-cadherin in HCC lines with different metastatic potential and normal cell lines were detected. The expression of FoxM1 was regulated by transfection of pcDNA3.1-FoxM1 and siRNA-FoxM1, the role of FoxM1 and Snail in EMT of HCC was investigated. Applying scratch assay and Transwell experiment, the effect of FoxM1 on invasion and mi- gration ability of cancer cells was detected. Results FoxM1 was highly expressed in HCC （F=29.617,18.037;P〈0.05）. The high expression of FoxM1 in FICC was negatively correlated with E-cadherin （r = --0.893, P〈0.05）, and positively correlated with that of Snail （r = 0.993, P〈0.05）. The scratch assay showed that down-regulation of FoxM1 expression could reduce the migration ability of liver cancer cells （t = 4.594, P〈0.05）, while up-regulation of its expression could increase the ability of its migration （t = -4.459, P〈0.05）. The Transwell experiment indicated that down-regulation of FoxM1 reduced the ability of invasion of the liver cancer cells, and up-regulation of FoxM1 increased the liver cancer cell invasion （t= -4.385,-4.950;P〈0.05）. Conclusion The high expression of FoxM1 in cells of hepatocellular carcinoma may promote the migration and invasion of the cells, and FoxM1 is likely to become a new target for therapy of liver cancer.