4.5 Article

Variant SNPs at the microRNA complementary site in the B7-H1 3'-untranslated region increase the risk of non-small cell lung cancer

Journal

MOLECULAR MEDICINE REPORTS
Volume 16, Issue 3, Pages -

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2017.6902

Keywords

B7-H1; single nucleotide polymorphism; microRNA; non-small cell lung cancer

Funding

  1. National Natural Science Foundation of China [31270940]
  2. Jiangsu Provincial Special Program of Medical Science [BL2012023]
  3. Clinical Medical Center of Suzhou [Szzx201502]
  4. Clinical Key Specialty Project of China

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Single nucleotide polymorphisms (SNPs) in microRNA-binding sites located in the 3'-untranslated region (UTR) of target genes can have an effect on the interaction of microRNA-mediated regulation, which results in changes in the expression levels of target genes ultimately associated with cancer risk and patient prognosis. However, the role of SNPs at the 3'-UTR of B7-H1 in the susceptibility of non-small cell lung cancer (NSCLC) remains to be fully elucidated. In the present study, SNPs with a minor allele frequency >10%, which were located at the microRNA complementary site in the PD-L1 3'-UTR, were selected via bioinformatic prediction using Ensembl and miRanda 2010. A total of three SNPs were selected, s2297136, rs4143815 and rs4742098, in the 3'-UTR of B7-H1. The rs2297136 and rs4742098 SNPs exhibited significant differences between 320 patients with NSCLC and 199 healthy individuals, respectively (P<0.001 and P=0.007). For the rs2297136 SNP, the AG genotype was significantly associated with evaluation of the risk of NSCLC, compared the AA genotype [odds ratio (OR)=2.287; 95% confidence interval (95% CI)=1.558-3.358]. Similarly, for the rs4742098 SNP, the AG genotype differed from the AA genotype on evaluation of the risk of NSCLC (OR=1.599; 95% CI=1.027-2.488). Dual-luciferase reporter assays showed that rs2297136 and rs4742098 in the B7-H1 3'-UTR contributed to the occurrence of NSCLC through disrupting the interaction between miR-296-5p, miR-138 and B7-H1 mRNA. These results indicated that genetic polymorphisms affecting the expression of B7-H1 modified cancer susceptibility.

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