Downregulated expression of CIAPIN1 may contribute to gastric carcinogenesis by accelerating cell proliferation and promoting cell cycle progression

Abstract

Our previous studies revealed that cytokine induced apoptosis inhibitor 1 (CIAPIN1), which was

reported to be essential in mouse definitive hematopoiesis, was related to multidrug resistance in

gastric cancer cells and that the distribution of CIAPIN1 in normal human tissues was similar to the

distribution of Ras. This study aimed to explore whether CIAPIN1 plays a role in gastric

carcinogenesis. Expression of CIAPIN1 in normal, inflammatory gastric mucosa, gastric precancerous

lesions and gastric adenocarcinoma was detected by immunohistochemistry and Western blotting and,

influence of CIAPIN1 on the proliferation of gastric cancer cells was investigated by ectopic

expression of CIAPIN1 and RNA interference (RNAi). Our immunohistochemical results

demonstrated that the expression of CIAPIN1 in gastric antral mucosa was progressively reduced

along the sequence of normal/inflammatory gastric mucosa-atrophy-intestinal

metaplasia-dysplasia-adenocarcinoma. The downregulation of CIAPIN1 in cancerous tissues was

further confirmed by Western blotting. No relationship between the expression level of CIAPIN1 and

the clinicopathological parameters such as age, gender, differentiation, TNM stage and the existence

of metastasis was found in gastric cancer patients. In in vitro cellular experiments, ectopic expression

of CIAPIN1 by cDNA transfection resulted in suppression of cell proliferation and inhibition of cell

cycle progression while knockdown of CIAPIN1 with siRNA accelerated cell proliferation and

promoted cell cycle progression in SGC7901 and MKN28 gastric cancer cells. These results suggest

that downregulated CIAPIN1 expression may contribute to gastric carcinogenesis by accelerating cell

proliferation and promoting cell cycle progression.