Casein kinase 2 interacting protein 1 positively regulates caudal-related homeobox 1 in intestinal-type gastric cancer
10.1097/CM9.0000000000000604
- Author:
Ma LIANG
1
;
Cao YING
;
Hu JIAN-JUN
;
Chu MING-LIANG
Author Information
1. Guizhou University School of Medicine
- Keywords:
Casein kinase 2 interacting protein 1;
Caudal-related homeobox 1;
Intestinal-type gastric cancer;
Intestinal metaplasia
- From:
Chinese Medical Journal
2020;133(2):154-164
- CountryChina
- Language:Chinese
-
Abstract:
Background:Gastric cancer (GC) is one of the most common malignancies,and intestinal-type GC is the main histopathologic type of GC in China.We previously reported that casein kinase 2 interacting protein 1 (CKIP-1) acts as a candidate tumor suppressor in intestinal-type GC.CKIP-1 participates in the regulation of multiple signaling pathways,including the Wnt/β-catenin pathway,of which caudal-related homeobox 1 (CDX1) may be a downstream target gene.The purpose of this study was to investigate the relationship between CKIP-1 and CDX1 in intestinal-type GC.Methods:Sixty-seven gastroscopy biopsy specimens and surgically resected gastric specimens were divided into four groups:gastric mucosa group,intestinal metaplasia (IM) group,dysplasia group,and intestinal-type GC group.The expression levels of CKIP-1 and CDX1 were detected in these groups and GC cell lines,and the correlations between these expression levels were analyzed.SGC7901 and BGC823 cells were divided into CKIP-1 shRNA groups and CKIP-1 over-expression groups,and CDX1 expression was detected.β-Catenin expression was detected in intestinal-type GC tissue samples and CKIP-1 shRNA and CKIP-1 over-expression SGC7901 cells,and its correlation with CKIP-1 expression in intestinal-type GC tissue was analyzed.The Wnt/β-catenin pathway inhibitor DKK-1 and activator LiCl were incubated with SGC7901 cells,BGC823 cells,and CKIP-1 shRNA and CKIP-1 over-expression SGC7901 and BGC823 cells,following which CDX1 and Ki-67 expression were detected.Results:The expression levels of CKIP-1 and CDX1 were lower in patients with intestinal-type GC than in patients with IM and dysplasia (both P ＜ 0.05).CKIP-1 and CDX1 expression levels were positively correlated in IM,dysplasia,and intestinal-type GC tissue and cell lines (r =0.771,P ＜ 0.01;r =0.597,P ＜ 0.01;r =0.654,P ＜ 0.01;r =0.811,P ＜ 0.01,respectively).CDX1 expression was decreased in the CKIP-1 shRNA groups and increased in the CKIP-1 over-expression groups of SGC7901 and BGC823 cells compared to that in the corresponding control groups (both P ＜ 0.05).CKIP-1 expression was negatively correlated with β-catenin expression in intestinal-type GC patients (r =-0.458,P ＜ 0.01).Compared to the control group,β-catenin expression was increased in the CKIP-1 shRNA SGC7901 cell group and decreased in the CKIP-1 over-expression SGC7901 cell group (P ＜ 0.05).CDX1 expression was increased in SGC7901 and BGC823 cells treated with DKK-1,DKK-1 increased CDX1 expression and decreased Ki-67 expression in the CKIP-1 shRNA group;the opposite result was observed in SGC7901 and BGC823 cells treated with LiCl,and LiCl decreased CDX1 expression and increased Ki-67 expression in the CKIP-1 over-expression group (both P ＜ 0.05).Conclusions:Through the Wnt/p-catenin signaling pathway,CKIP-1 may positively regulate CDX1 in intestinal-type GC.
