Objective: 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