The association analysis of lncRNA HOTAIR genetic variants and gastric cancer risk in a Chinese population
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Mulong Du1,*, Weizhi Wang2,*, Hua Jin3,*, Qiaoyan Wang1, Yuqiu Ge1, Jiafei Lu1, Gaoxiang Ma1, Haiyan Chu1,4, Na Tong1,4, Haixia Zhu3, Meilin Wang1,4, Fulin Qiang3, Zhengdong Zhang1,4
1Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China
2Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
3Core Laboratory, Nantong Tumor Hospital, Nantong, China
4Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
*These authors have contributed equally to this work
Zhengdong Zhang, e-mail: [email protected]
Keywords: long noncoding RNA, HOTAIR, genetic variants, gastric cancer
Received: May 12, 2015 Accepted: August 24, 2015 Published: September 04, 2015
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.
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