CARP is a potential tumor suppressor in gastric carcinoma and a single-nucleotide polymorphism in CARP gene might increase the risk of gastric carcinoma.

BACKGROUND:The caspase-associated recruitment domain-containing protein is expressed in almost all tissues. Recently, the tumor-suppressive function of was discovered and attracted increasing attention. This study aimed to investigate the role of Cduanyu37 in the carcinogenesis of human gastric carcinoma. METHODOLOGY/PRINCIPAL FINDINGS:Compared with normal gastric tissue, the downregulation of Cduanyu37 expression was observed in gastric carcinoma tissue by cDNA array and tissue microarray assay. In vitro, the gastric carcinoma cell line (BGC-823) was stably transfected with or plus Cduanyu37 siRNA, and we used MTT, flow cytometry, cell migration on type I collagen, cell-matrix adhesion assay and western blot analysis to investigate the potential anti-tumor effects of The data showed that overexpressing Cduanyu37 suppressed the malignancy of gastric carcinoma BGC-823 cell line, including significant increases in apoptosis, as well as obvious decreases in cell proliferation, migration, adhesion ability, and tumor growth. The tumor-suppressive effects of Cduanyu37 were almost restored by siRNA-directed Cduanyu37 silence. In addition, overexpression of Cduanyu37 induced G1 arrest, decreased the expressions of cyclin E and CDK2, and increased the expressions of p27, p53 and p21. In vivo, the tumor-suppressive effect of Cduanyu37 was also verified. A single-nucleotide polymorphism (SNP) genotype of Cduanyu37 (rs2297882) was located in the Kozak sequence of the Cduanyu37 gene. The reporter gene assay showed that rs2297882 TT caused an obvious downregulation of activity of Cduanyu37 gene promoter in BGC-823 cells. Furthermore, the association between rs2297882 and human gastric carcinoma susceptibility was analyzed in 352 cases and 889 controls. It displayed that the TT genotype of rs2297882 in the Cduanyu37 gene was associated with an increased risk of gastric is a potential tumor suppressor of gastric carcinoma and the rs2297882 C>T phenotype of Cduanyu37 may serve as a predictor of gastric carcinoma.

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