Hu Hua, Zhang Linlin, Teng Geling, Wu Yanhua, Chen Ying
The Respiratory Department, Shandong Provincial Chest Hospital, Jinan, Shandong, People's Republic of China.
The Clinical Laboratory of Shandong Provincial Chest Hospital, Jinan, Shandong, People's Republic of China.
Int J Chron Obstruct Pulmon Dis. 2015 Aug 17;10:1641-9. doi: 10.2147/COPD.S83596. eCollection 2015.
The objective of the present study was to explore the molecular mechanism by which a single nucleotide polymorphism (rs712) interferes with interaction between 3'-untranslated region (3'-UTR) of KRAS and let-7g, and its association with development of lung cancer in the patients with COPD.
In this study, we confirmed that KRAS is a target of let-7g in lung cancer cells, and that introduction of rs712 minor allele into 3'-UTR significantly compromised the miRNA/mRNA interaction by using a luciferase reporter system. Additionally, a total of 35 lung tissue samples were obtained (TT:17, TG:12, GG:6), and let-7g and KRAS expression levels were determined.
We showed that let-7g level was similar between groups, and the concentration of KRAS in GG genotype group was significantly higher than in TT or GT genotype group. Meanwhile, we found COPD patients with GG genotype had significantly higher risk for lung cancer (odds ratio OR =6.83, P=0.0081), compared with TT and GT genotypes.
Our study demonstrated that KRAS 3'-UTR rs712 polymorphism interfered with miRNA/mRNA interaction, and showed that the minor allele was associated with an elevated risk for development of lung cancer in COPD.
本研究旨在探讨单核苷酸多态性（rs712）干扰KRAS基因3'非翻译区（3'-UTR）与let-7g相互作用的分子机制，及其与慢性阻塞性肺疾病（COPD）患者肺癌发生的相关性。
在本研究中，我们利用荧光素酶报告系统证实KRAS是肺癌细胞中let-7g的靶基因，并且将rs712次要等位基因导入3'-UTR会显著损害miRNA/mRNA相互作用。此外，共获取了35份肺组织样本（TT型：17份，TG型：12份，GG型：6份），并测定了let-7g和KRAS的表达水平。
我们发现各基因型组间let-7g水平相似，GG基因型组中KRAS的浓度显著高于TT或GT基因型组。同时，我们发现与TT和GT基因型相比，GG基因型的COPD患者患肺癌的风险显著更高（优势比OR = 6.83，P = 0.0081）。
我们的研究表明KRAS基因3'-UTR rs712多态性干扰了miRNA/mRNA相互作用，并表明次要等位基因与COPD患者肺癌发生风险升高相关。
