XPG is Modulated by miR-4715-3p and rs873601 Genotypes in Lung Cancer

Abstract

WeiLing Yu,1 JinJian Yao,2 Pengfei Lyu,3 Jing Zhou,4 Xiaoxi Chen,4 Xiaoran Liu,5 Sha Xiao4 1Oncology Department, Haikou City People’s Hospital, Haikou, 570208, Hainan, People’s Republic of China; 2Emergency Department, Hainan General Hospital Affiliated to Hainan Medical University, Haikou, 570311, Hainan, People’s Republic of China; 3Department of Breast-Thoracic Tumor Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, 570102, Hainan, People’s Republic of China; 4Department of Environmental and Occupational Health, School of Public Health, Hainan Medical University, Haikou, 571199, Hainan, People’s Republic of China; 5Emergency Department, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, People’s Republic of ChinaCorrespondence: Xiaoran LiuEmergency Department, The First Affiliated Hospital of Hainan Medical University, Longhua District, Longhua Road No.31, Haikou, Hainan, 570102, People’s Republic of ChinaTel [phone]Email [email protected] XiaoDepartment of Environmental and Occupational Health, School of Public Health, Hainan Medical University, Longhua District, Xueyuan Road No.3, Haikou, 571199, People’s Republic of ChinaTel [phone]Email [email protected]: XPG (Xeroderma pigmentosum group G, XPG), a single strand-specific DNA endonuclease in the nucleotide excision repair pathway, has been implicated in lung cancer. Potentially functional rs873601 in XPG is consistently associated with gastrointestinal cancer, and miR-4715-3p, targeting 3UTR of XPG, also influences the process of gastrointestinal carcinogenesis, however, the relationships between XPG and miR-4715-3p and rs873601 in lung cancer have not been elucidated.Methods: A case-control study included 264 lung cancer patients and 264 cancer-free healthy controls and was designed to determine the relationships between rs873601 and lung cancer and the effect of miR-4715-3p on XPG expression in lung cancer. Fifty matched cases and controls were randomly selected from the lung cancer and control groups to assess the relationships between the expression levels of miR-4715-3p and XPG determined by using qRT-PCR. The association of rs873601 with lung cancer was analyzed by mass spectrometry, and function prediciton of rs873601 genotypes explored by web-based bioinformatics.Results: miR-4715-3p in the lung cancer group was significantly increased compared with that in the control group (P = 0.011), upregulation of miR-4715-3p correlated with an increase in XPG mRNA (r = 0.399, P < 0.05) in the lung cancer group. The AA genotype was associated with increased risk of lung cancer compared with the AG and GG genotypes of rs873601 (AG vs AA: OR = 0.231, 95% CI: 0.155– 0.345, P < 0.001 GG vs AA: OR = 0.300, 95% CI: 0.131– 0.719, P = 0.003). The genetic association remained significant after adjustment for age, sex, smoking, and drinking, and rs873601-AA was associated with an increase in XPG mRNA in the lung cancer group. The results of web-based bioinformatics analysis indicated rs873601 genotypes might change XPG-RNA stability and bindability between XPG and miR-4715-3p.Conclusion: Our data characterized that miR-4715-3p and rs873601 genotypes modified XPG expression in lung cancer. These findings may help to elucidate the mechanisms governing lung cancer.Keywords: miR-4715-3p, XPG, rs873601, lung cancer

Keywords

• mir-4715-3p
• xpg
• rs873601
• lung cancer