A functional variant at miR-24 binding site in B7-H2 alters susceptibility to gastric cancer in a Chinese Han population

Mol Immunol. 2013 Nov;56(1-2):98-103. doi: 10.1016/j.molimm.2013.04.010. Epub 2013 May 18.

Abstract

A number of single nucleotide polymorphisms (SNPs) within the 3'-UTR of genes have been proved to be contributed to the risk of cancers. Here, we determined an SNP rs4819388 in the 3'-UTR of B7-H2 gene in 183 gastric cancer patients and 348 healthy controls by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Statistical analysis results showed that the rs4819388 genotypes were significantly related to the occurrence of gastric cancer. Compared with the GG homozygotes, the GA heterozygotes were significantly more prevalent in the patients (OR=1.60, 95%CI=1.08-2.37). In addition, the A allelic frequencies were significantly higher than that of the G allele in the patients with lymphatic metastasis (p=0.034) and/or advanced TNM stage (p=0.032). Dual-luciferase reporter assays showed that miR-24 inhibited the expression of B7-H2 through binding with the B7-H2 3'-UTR, and this inhibitory role of miR-24 was impacted by rs4819388. Our findings suggest that the SNP rs4819388 in B7-H2 3'-UTR, through disrupting the regulatory role of miR-24 on B7-H2 expression, contributes to the occurrence of gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Alleles
  • Animals
  • Asian People / genetics
  • Base Sequence
  • Binding Sites / genetics
  • CHO Cells
  • China
  • Cricetinae
  • Cricetulus
  • DNA Mutational Analysis
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Inducible T-Cell Co-Stimulator Ligand / genetics*
  • Logistic Models
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide*
  • Stomach Neoplasms / ethnology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology

Substances

  • 3' Untranslated Regions
  • ICOSLG protein, human
  • Inducible T-Cell Co-Stimulator Ligand
  • MIRN24 microRNA, human
  • MicroRNAs