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

WeiLing Yu; JinJian Yao; Pengfei Lyu; Jing Zhou; Xiaoxi Chen; Xiaoran Liu; Sha Xiao

doi:10.2147/CMAR.S294365

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

Cancer Manag Res. 2021 Apr 19:13:3417-3427. doi: 10.2147/CMAR.S294365. eCollection 2021.

Authors

WeiLing Yu¹, JinJian Yao², Pengfei Lyu³, Jing Zhou⁴, Xiaoxi Chen⁴, Xiaoran Liu⁵, Sha Xiao⁴

Affiliations

¹ Oncology Department, Haikou City People's Hospital, Haikou, 570208, Hainan, People's Republic of China.
² Emergency Department, Hainan General Hospital Affiliated to Hainan Medical University, Haikou, 570311, Hainan, People's Republic of China.
³ Department of Breast-Thoracic Tumor Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, 570102, Hainan, People's Republic of China.
⁴ Department of Environmental and Occupational Health, School of Public Health, Hainan Medical University, Haikou, 571199, Hainan, People's Republic of China.
⁵ Emergency Department, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, People's Republic of China.

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: XPG; lung cancer; miR-4715-3p; rs873601.