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

Abstract

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

Acknowledgments

Weiling Yu and Jinjian Yao are co-first authors in this manuscript. This study was supported by the National Natural Science Foundation of China (No 81660550), the Province Natural Science Foundation of Hainan (No 814292 and No 310150), and the Foundation for Fostering Talents of Hainan Medical University (No HYPY201911).

Disclosure

The authors state that they have no conflicts of interest to disclose.