CDX2和Reg IV在胃癌中的表达及相关性
CDX2 and Reg IV expression and correlation in gastric cancer.
作者信息
Chai Dandan, Du Huifen, Li Kesheng, Zhang Xueliang, Li Xiaoqin, Zhao Xiaoning, Lian Xiaowen, Xu Yang
机构信息
Department of Medicine Biotechnology, Gansu Provincial Academic Institute for Medical Research, Xiaoxihu East Street No. 2, Lanzhou, 730050, Gansu, China.
Department of Internal Medicine, Gansu Provincial Cancer Hospital, Lanzhou, Gansu, China.
出版信息
BMC Gastroenterol. 2021 Feb 27;21(1):92. doi: 10.1186/s12876-021-01678-9.
BACKGROUND
Ectopic expression of CDX2 is associated with the development and progression of gastric cancer. Previous studies showed that CDX2 may be an upstream regulator of Reg IV expression in gastric cancer, and our previous report showed that Reg IV upregulated SOX9 expression and enhanced cell migration and invasion in gastric cancer cells. However, the regulatory roles of CDX2 have not been clarified in gastric cancer, and the correlation between CDX2 and Reg IV requires further study.
METHODS
CDX2 and Reg IV were examined in gastric cancer specimens and paired adjacent tissues via real-time PCR and immunohistochemistry (IHC). The association between CDX2 and Reg IV was assessed using the χ-test and Spearman's rank correlation. To verify their relationship, knockdown and exogenous expression of CDX2 or Reg IV were performed in AGS and MKN-45 gastric cancer cells, and their expression was subsequently analyzed via a real-time PCR and western blotting. Wound-healing and Transwell assays were used to examine migration and invasion in AGS and MKN-45 cells following CDX2 silencing or overexpression.
RESULTS
A positive correlation was observed between CDX2 and Reg IV expression at the mRNA and protein levels in gastric cancer tissues. CDX2 silencing significantly downregulated Reg IV expression, and CDX2 overexpression significantly upregulated Reg IV expression in AGS and MKN-45 cells. Neither Reg IV silencing nor overexpression had any effect on CDX2 protein expression in AGS or MKN-45 cells, even though both affected the expression of CDX2 mRNA. Functionally, CDX2 silencing significantly inhibited cell migration and invasion, and CDX2 overexpression significantly promoted cell migration and invasion in AGS and MKN-45 cells.
CONCLUSIONS
Our findings demonstrate that CDX2 expression was positively correlated with that of Reg IV in gastric cancer, and CDX2 promoted cell migration and invasion through upregulation of Reg IV expression in AGS and MKN-45 cells.
背景
CDX2的异位表达与胃癌的发生发展相关。既往研究表明，CDX2可能是胃癌中Reg IV表达的上游调节因子，且我们之前的报告显示Reg IV上调SOX9表达并增强胃癌细胞的迁移和侵袭能力。然而，CDX2在胃癌中的调节作用尚未阐明，CDX2与Reg IV之间的相关性有待进一步研究。
方法
通过实时PCR和免疫组织化学（IHC）检测胃癌标本及配对的癌旁组织中CDX2和Reg IV的表达情况。采用χ检验和Spearman等级相关性分析评估CDX2与Reg IV之间的关联。为验证它们之间的关系，在AGS和MKN-45胃癌细胞中进行CDX2或Reg IV的敲低和外源性表达，随后通过实时PCR和蛋白质印迹法分析其表达情况。采用划痕实验和Transwell实验检测CDX2沉默或过表达后AGS和MKN-45细胞的迁移和侵袭能力。
结果
在胃癌组织中，CDX2与Reg IV在mRNA和蛋白质水平的表达呈正相关。在AGS和MKN-45细胞中，CDX2沉默显著下调Reg IV表达，而CDX2过表达显著上调Reg IV表达。尽管Reg IV的沉默和过表达均影响CDX2 mRNA的表达，但对AGS或MKN-45细胞中CDX2蛋白质表达均无影响。在功能上，CDX2沉默显著抑制AGS和MKN-45细胞的迁移和侵袭，而CDX2过表达显著促进其迁移和侵袭。
结论
我们的研究结果表明，在胃癌中CDX2的表达与Reg IV呈正相关，且CDX2通过上调AGS和MKN-45细胞中Reg IV的表达促进细胞迁移和侵袭。
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