A functional variant at miR-132-3p, miR-212-3p, and miR-361-5p binding site in CD80 gene alters susceptibility to gastric cancer in a Chinese Han population

摘要

A number of single-nucleotide polymorphisms within the 3'-UTR of genes have been shown to relate to the occurrence of cancers. In this study, by using polymerase chain reaction-restriction fragment length analysis method, we determined an SNP rs1599795 in the 3'-UTR of CD80 gene in 183 gastric cancer patients and 348 healthy controls. Statistical analysis results showed that SNP rs1599795 genotypes were significantly correlated with the risk of gastric cancer. Compared with the AA homozygotes, the TA heterozygotes were significantly more prevalent in the patients (OR 1.44, 95 % CI 0.98-2.11) with a larger tumor size (P = 0.001), deeper infiltration (P = 1.5 x 10(-5)), higher possibility of lymph node metastasis (P = 0.003), and more in the late stage (TNM stage III and IV; P = 0.003); the TT homozygotes had larger tumor size (P = 0.001) and lower degree of differentiation (P = 2.2 x 10(-4)). Dual-luciferase reporter assays showed that miR-132-3p, miR-212-3p, and miR-361-5p inhibited the expression of CD80 through binding with the CD80 3'-UTR, and this inhibitory role of miR-132-3p, miR-212-3p, and miR-361-5p was impacted by rs1599795. Our findings have shown that the SNP rs1599795 in CD80 3'-UTR, through disrupting the regulatory role of miR-132-3p, miR-212-3p, and miR-361-5p in CD80 expression, contributed to the occurrence of gastric cancer.