婆罗双树样基因4对肝癌细胞侵袭转移和上皮间质转化的影响

SAL-like 4 promotes hepatocellular carcinoma invasion and metastasis associated with the induction of epithelial-mesenchymal transition

目的:探讨婆罗双树样基因4(SALL4)对肝细胞癌(hepatocellular carcinoma,HCC)侵袭转移和上皮间质转化(EMT)的影响。方法:构建过表达和靶向干扰SALL4的稳定HCC细胞株,Transwell小室实验检测肝癌细胞的迁移侵袭能力,实时荧光定量PCR和Western blot检测SALL4和EMT相关分子的mRNA和蛋白表达水平。结果:Transwell小室迁移侵袭实验证明,SALL4增强肝癌细胞迁移侵袭能力,SALL4过表达Huh7细胞E-cadherin mRNA和蛋白水平均降低,而Vimentin mRNA和蛋白水平均增加;反之,与对照组比较,转染SALL4-siRNA的HepG2细胞E-cadherin mRNA和蛋白水平均增加,而Vimentin mRNA和蛋白水平均降低。随着SALL4表达上调,Huh7细胞的Twist、Snail、Slug mRNA水平显著升高,反之,干扰SALL4基因表达的HepG2细胞Twist、Snail、Slug mRNA水平下降。结论:SALL4对肝癌细胞侵袭转移能力和EMT有重要影响,可能成为靶向EMT控制肝癌侵袭转移的策略之一。

Objective：To examine whether SAL- like 4 （SALL4） had any effect on hepatocellular carcinoma （HCC） invasion, metastasisandepithelial - mesenehymal transition （EMT）. Methods： Transwell assays were per- formed to assess the migration and invasiveness of HCC ceils following transfection with eNDA or the siRNA of SALIA. The expression of SALL4 and EMT molecules were assessed by using qRT - PCR and Western blot. Results： We demonstrated that SALL4 overexpression enhanced HCC cell migration and invasion, whereas knockdown of SALIA showed the opposite effect. Moreover, E - eadherin were reduced but ~imentin were increased at mRNA and protein levels in SALIA overexpression Huh7 cells. In contrast, E - cadherin were significantly increased but Vimentiu were reduced in SALL4 - knockdown HepG2 cells. Furthermore, genetic modulation of SALL4 altered the mRNA ex- pression of EMT - related regulators, including Snail, Slug, and Twist. Conclusion： Our data indicated that SALL4 promotes HCC invasion and metastasis associated with the induction of EMT,this suggests inhibition of SALL4 as a potential therapeutic strategy for HCC.