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

Du,Wenwen; Zhu,Jianjie; Chen,Yanbin; Zeng,Yuanyuan; Shen,Dan; Zhang,Nan; Ning,Weiwei; Liu,Zeyi; Huang,Jian‑An

doi:10.3892/mmr.2017.6902

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

Authors:
- Wenwen Du
- Jianjie Zhu
- Yanbin Chen
- Yuanyuan Zeng
- Dan Shen
- Nan Zhang
- Weiwei Ning
- Zeyi Liu
- Jian‑An Huang
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Affiliations: Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
Published online on: June 30, 2017 https://doi.org/10.3892/mmr.2017.6902
Pages: 2682-2690
Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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