Yu WeiLing, Yao JinJian, Lyu Pengfei, Zhou Jing, Chen Xiaoxi, Liu Xiaoran, Xiao Sha
Oncology Department, Haikou City People's Hospital, Haikou, 570208, Hainan, People's Republic of China.
Emergency Department, Hainan General Hospital Affiliated to Hainan Medical University, Haikou, 570311, Hainan, People's Republic of China.
Cancer Manag Res. 2021 Apr 19;13:3417-3427. doi: 10.2147/CMAR.S294365. eCollection 2021.
(Xeroderma pigmentosum group G, ), a single strand-specific DNA endonuclease in the nucleotide excision repair pathway, has been implicated in lung cancer. Potentially functional rs873601 in is consistently associated with gastrointestinal cancer, and miR-4715-3p, targeting 3UTR of , also influences the process of gastrointestinal carcinogenesis, however, the relationships between and miR-4715-3p and rs873601 in lung cancer have not been elucidated.
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 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 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.
miR-4715-3p in the lung cancer group was significantly increased compared with that in the control group ( = 0.011), upregulation of miR-4715-3p correlated with an increase in mRNA (r = 0.399, <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, <0.001 GG vs AA: OR = 0.300, 95% CI: 0.131-0.719, = 0.003). The genetic association remained significant after adjustment for age, sex, smoking, and drinking, and rs873601-AA was associated with an increase in 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.
Our data characterized that miR-4715-3p and rs873601 genotypes modified expression in lung cancer. These findings may help to elucidate the mechanisms governing lung cancer.
XPG（着色性干皮病G组）是核苷酸切除修复途径中的一种单链特异性DNA内切酶，与肺癌有关。XPG中潜在功能性的rs873601一直与胃肠道癌相关，靶向XPG 3'UTR的miR-4715-3p也影响胃肠道癌变过程，然而，XPG与miR-4715-3p及rs873601在肺癌中的关系尚未阐明。
一项病例对照研究纳入了264例肺癌患者和264例无癌健康对照，旨在确定rs873601与肺癌的关系以及miR-4715-3p对肺癌中XPG表达的影响。从肺癌组和对照组中随机选取50对匹配的病例和对照，采用qRT-PCR检测miR-4715-3p和XPG的表达水平，以评估它们之间的关系。通过质谱分析rs873601与肺癌的关联，并利用基于网络的生物信息学探索rs873601基因型的功能预测。
肺癌组的miR-4715-3p显著高于对照组（P = 0.011），肺癌组中miR-4715-3p的上调与XPG mRNA的增加相关（r = 0.399，P<0.05）。与rs873601的AG和GG基因型相比，AA基因型与肺癌风险增加相关（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）。在调整年龄、性别、吸烟和饮酒因素后这种遗传关联仍然显著，且rs873601 - AA与肺癌组中XPG mRNA的增加相关。基于网络的生物信息学分析结果表明，rs873601基因型可能会改变XPG - RNA的稳定性以及XPG与miR-4715-3p之间的结合能力。
我们的数据表明miR-4715-3p和rs873601基因型在肺癌中改变了XPG的表达。这些发现可能有助于阐明肺癌发生的机制。
