The association analysis of lncRNA HOTAIR genetic variants and gastric cancer risk in a Chinese population.
The association analysis of lncRNA HOTAIR genetic variants and gastric cancer risk in a Chinese population.
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中国人群lncRNA HOTAIR基因变异与胃癌风险的关联分析
DOI：
10.18632/oncotarget.5158
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发表时间：
2015-10-13
期刊：
影响因子：
--
通讯作者：
Zhang Z
中科院分区：
文献类型：
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作者：
Du M;Wang W;Jin H;Wang Q;Ge Y;Lu J;Ma G;Chu H;Tong N;Zhu H;Wang M;Qiang F;Zhang Z
HOX转录本反义基因间RNA（HOTAIR）是一种已知的长链非编码RNA，与多种肿瘤的发生、发展密切相关。在胃癌中的异位表达及其生物学功能已被观察到。在这项研究中，我们进行了一个两阶段的病例对照研究，以评估HOTAIR的遗传变异是否与胃癌的风险。我们发现，单核苷酸多态性（SNP）rs 4759314与胃癌风险增加显著相关，其比值比（OR）为1.39 [95%置信区间（CI）= 1.13-1.71，P = 0.002]。进一步的功能实验显示，HOTAIR和HOXC 11在胃癌组织中的表达存在等位基因特异性效应，其中AG基因型个体的HOTAIR和HOXC 11表达明显高于AA基因型个体;内含子启动子活性也存在这种效应，其中G等位基因的启动子活性明显高于A等位基因。有趣的是，我们发现了一个新的潜在的癌基因HOXC 11在胃癌的发病机制与胃癌组织中的差异表达的关联分析与候选基因策略。提示HOTAIR基因rs 4759314多态性可作为预测胃癌的潜在生物标志物，HOXC 11在胃癌发病中的作用有待进一步研究。
The HOX transcript antisense intergenic RNA (HOTAIR), a well-known long noncoding RNA, is involved in pathogenesis and progress of multiple tumors. Its ectopic expression and biological functions have been observed in gastric cancer. In this study, we conducted a two-stage case-control study to evaluate whether genetic variations of HOTAIR were associated with gastric cancer risk. We identified that a single nucleotide polymorphism (SNP) rs4759314 was significantly associated with the increased gastric cancer risk with an odds ratio (OR) of 1.39 [95% confidence interval (CI) = 1.13–1.71, P = 0.002] in the combined sets. Further functional experiments revealed the allele-specific effects on HOTAIR and HOXC11 expressions in gastric cancer tissues, of which HOTAIR and HOXC11 expressions of individuals carrying with AG genotype were much higher than those with AA genotype; similarly, the effects occurred in intronic promoter activities, of which the promoter activity of G allele was more pronounced than that of A allele. Interestingly, we identified a novel potential oncogene HOXC11 in gastric cancer pathogenesis with differential expression in gastric cancer tissues by association analysis with candidate gene strategy. These results suggest that SNP rs4759314 of HOTAIR acts as a potential biomarker for predicting gastric cancer, and the role of HOXC11 in gastric cancer etiology is warranted to further investigation.