Oncotarget

Research Papers:

MiR-146a polymorphism correlates with lung cancer risk in Chinese nonsmoking females

Zhihua Yin _, Zhigang Cui, Yangwu Ren, Lingzi Xia, Hang Li and Baosen Zhou

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Oncotarget. 2017; 8:2275-2283. https://doi.org/10.18632/oncotarget.13722

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Abstract

Zhihua Yin1,2, Zhigang Cui3, Yangwu Ren1,2, Lingzi Xia1,2, Hang Li1,2 and Baosen Zhou1,2

1 Department of Epidemiology, School of Public Health, China Medical University, Shenyang, PR China

2 Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, PR China

3 School of Nursing, China Medical University, Shenyang, China

Correspondence to:

Zhihua Yin, email:

Baosen Zhou, email:

Keywords: lung cancer, microRNA, single nucleotide polymorphism, genetic susceptibility, gene expression

Received: July 11, 2016 Accepted: November 24, 2016 Published: November 30, 2016

Abstract

This study provides evidence that the common rs2910164 polymorphism in miR-146a strongly correlates with lung cancer risk in nonsmoking females in northeast China. The genotypes of miR-146a rs2910164 were determined in 1131 patients with lung cancer and 1003 healthy control subjects. Tissue samples were used to evaluate the association between miRNA expression and lung cancer risk as well as the correlation between rs2910164 genotypes and miR-146a expression. The secondary structures of the wild-type and variant miR-146a sequences were predicted, and luciferase-based target assays were used to test whether miR-146a bound to tumor necrosis factor receptor associated factor 6 (TRAF6) mRNA. Individuals carrying heterozygous CG genotype of miR-146a rs2910164 had less risk of lung cancer than those carrying homozygous wild CC genotype (OR = 0.76, 95% CI = 0.60-0.98, P = 0.032). We found no significant association between miR-146a expression and lung cancer risk. MiR-146a expression differed in those carrying the CC genotype as compared with the CG or the GG genotype (P = 0.032 and 0.001), and the secondary structure of the C allele differed slightly from the G allele. Significantly lower levels of luciferase activity were observed when the TRAF6 3′UTR was cotransfected with miR-146a-3p carrying the rs2910164 C allele (P = 0.001). Thus, miR-146a rs2910164 polymorphism may influence susceptibility to lung cancer in Chinese nonsmoking females through targeting TRAF6.


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