Journal Article

Genetic polymorphism at miR-181a binding site contributes to gastric cancer susceptibility

Yong Lin, Yuqiang Nie, Jing Zhao, Xi Chen, Min Ye, Yingfei Li, Yanlei Du, Jie Cao, Bo Shen and Yuyuan Li

in Carcinogenesis

Volume 33, issue 12, pages 2377-2383
Published in print December 2012 | ISSN: 0143-3334
Published online September 2012 | e-ISSN: 1460-2180 | DOI:
Genetic polymorphism at miR-181a binding site contributes to gastric cancer susceptibility

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Recent evidences show that genetic polymorphisms falling in miRNA binding sites can alter the strength of miRNA binding and disturb miRNA-mediated posttranscriptional regulation. Our study aimed to investigate the role of single-nucleotide polymorphisms (SNPs) in putative miRNA binding sites in gastric cancer (GC). Based on microarray and quantitative reverse transcription PCR analyses, we found that miR-181a was significantly upregulated in GC tissues. Bioinformatics survey was used to explore SNPs within miR-181a binding sites. Three SNPs were genotyped in a case–control study (500 cases and 502 controls). The T allele genotypes (rs12537CT and TT) of MTMR3 were found associated with significantly increased GC risk [adjusted odds ratio 1.72, 95% confidence interval (CI) 1.36–2.16, P = 3.99×10–5] and poor overall survival [hazard ratio (HR) 1.38, 95% CI 1.03–1.83, P = 0.029], although they were not an independent prognostic factor in multivariate Cox regression analysis (HR 1.28, 95% CI 0.95–1.72, P = 0.11). We further demonstrated that the rs12537CT genotype carriers had lower MTMR3 mRNA expression levels than CC genotype carriers in GC tissues (P = 0.013), whereas no significant difference in miR-181a expression levels was found (P = 0.135). Luciferase assay revealed that miR-181a directly targeted MTMR3, and its suppressive effect was enhanced when the rs12537C allele was substituted by T variant, although the difference was not significant (P = 0.055). Our study suggested that rs12537 is associated with susceptibility and prognosis of GC in southern Han Chinese, and miR-181a and its target gene MTMR3 play important roles in GC.

Journal Article.  6414 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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