Oncotarget

Research Papers:

Associations between genetic variants located in mature microRNAs and risk of lung cancer

Dengrui Li, Guiyun Zhu, Hongqin Di, Hui Li, Xinyan Liu, Min Zhao, Zhihua Zhang and Yonghui Yang _

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Oncotarget. 2016; 7:41715-41724. https://doi.org/10.18632/oncotarget.9566

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Abstract

Dengrui Li1,*, Guiyun Zhu2,*, Hongqin Di3, Hui Li4, Xinyan Liu5, Min Zhao6, Zhihua Zhang7, Yonghui Yang2

1Department of General Internal Medicine, Chest Hospital of Hebei Province, Lung Cancer Prevention and Control Center of Hebei Province, Shijiazhuang, Hebei, China, 050041

2Department of Pathology, Chest Hospital of Hebei Province, Lung Cancer Prevention and Control Center of Hebei Province, Shijiazhuang, Hebei, China, 050041

3Clinical Laboratory, Chest Hospital of Hebei Province, Lung Cancer Prevention and Control Center of Hebei Province, Shijiazhuang, Hebei, China, 050041

4Department of Thoracic Surgery, Chest Hospital of Hebei Province, Lung Cancer Prevention and Control Center of Hebei Province, Shijiazhuang, Hebei, China, 050041

5The First Department of Oncology, Chest Hospital of Hebei Province, Lung Cancer Prevention and Control Center of Hebei Province, Shijiazhuang, Hebei, China, 050041

6The Second Department of Oncology, Chest Hospital of Hebei Province, Lung Cancer Prevention and Control Center of Hebei Province, Shijiazhuang, Hebei, China, 050041

7Medical Department, Chest Hospital of Hebei Province, Lung Cancer Prevention and Control Center of Hebei Province, Shijiazhuang, Hebei, China, 050041

*These authors contributed equally to this work

Correspondence to:

Yonghui Yang, email: yangyonghuihb@126.com

Keywords: microRNAs, lung cancer, variant

Received: January 17, 2016     Accepted: May 12, 2016     Published: May 24, 2016

ABSTRACT

MiRNAs have been focused for their wide range of biological regulatory functions. Previous studies have suggested that individual miRNAs could influence tumorigenesis through their regulation of specific proto-oncogenes and tumor suppressor genes. This study was implemented to investigate the associations between SNPs in mature microRNAs (miRNAs) and development of lung cancer in a two-stage, case-control study, followed by some functional validations. First, 11 SNPs were analyzed in a case-control study of lung cancer, and the significant results were validated in an additional population. Our results showed that rs3746444 in mir-499 (allele C vs T: OR = 1.33; 95% CI = 1.15–1.54; P = 1.2 × 10–4) and rs4919510 in mir-608 (allele G vs C: OR = 1.27; 95% CI= 1.13–1.43; P = 5.1 × 10–5) were significantly associated with increased risk of lung cancer. Rs3746444 in mir-499 was also significantly associated with poor survival of lung cancer (HR, 1.35; 95% CI, 1.15–1.58; P = 0.0002). The expression levels of mir-499 and mir-608 were significantly lower than those of adjacent normal tissues (P < 0.0005), and the carriers of minor alleles have lower expression levels of mir-499 and mir-608 than those of major alleles (P < 0.001). These findings indicated that rs3746444 in mir-499 and rs4919510 in mir-608 might play a substantial role in the susceptibility to lung cancer.


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