Shizhi Wang1, Chunye Lv2, Hua Jin3, Ming Xu4, Meiyun Kang4, Haiyan Chu4, Na Tong4, Dongmei Wu4, Haixia Zhu5, Weida Gong6, Qinghong Zhao7, Guoquan Tao8, Jianwei Zhou9, Zhengdong Zhang10, Meilin Wang11. 1. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China; Southeast University, School of Public Health, Ministry of Education, Key Laboratory of Environmental Medicine and Engineering, 87 Dingjiaqiao Street, Nanjing, China. 2. Department of General Surgery, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China. 3. Core Laboratory, Nantong Tumor Hospital, Nantong, China. 4. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. 5. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China; Core Laboratory, Nantong Tumor Hospital, Nantong, China. 6. Department of General Surgery, Yixing Cancer Hospital, Yixing, China. 7. Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. 8. Department of General Surgery, Huai-An First People's Hospital Affiliated to Nanjing Medical University, Huai-An, China. 9. Department of Molecular Cell Biology and Toxicology, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China. 10. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. Electronic address: drzdzhang@gmail.com. 11. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. Electronic address: mwang@njmu.edu.cn.
Abstract
BACKGROUND: Global miRNA expression profile has been widely used to characterize human cancers. It is well established that genetic variants in miRNAs can modulate miRNA biogenesis and disease risk. METHODS: Genome-wide miRNA microarray was employed for assessment of miRNA expression profile of gastric adenocarcinoma (GAC). The variants of significantly dysregulated miRNA were genotyped in test (715 cases and 804 controls) and validation (940 cases and 1050 controls) subject sets. RESULTS: MiRNA microarray revealed that 12 miRNAs including miR-107 significantly dysregulated in GAC tissues. The sequencing of the promoter of miR-107 identified 3 SNPs (rs11185777, rs78591545, and rs2296616) with minor allele frequency (MAF)>5%. Analyzing their association with GAC risk and prognosis revealed that the C allele of rs2296616 (T>C) was significantly associated with the decreased risk of GAC among the test, validation and combined sets (TC/CC vs. TT, adjusted OR=0.39, 95% CI=0.31-0.49 for the combined set). However, the C allele was related to an unfavorable prognosis of Cardia GAC (CGAC) (adjusted HR=1.49, 95% CI=1.01-2.20). In vivo evidence showed that the individuals with the rs2296616C allele had lower miR-107 expression compared with the homozygous T allele carriers. CONCLUSION: miR-107 is dysregulated in GAC pathogenesis and the SNP rs2296616 may play a role in the process.
BACKGROUND: Global miRNA expression profile has been widely used to characterize humancancers. It is well established that genetic variants in miRNAs can modulate miRNA biogenesis and disease risk. METHODS: Genome-wide miRNA microarray was employed for assessment of miRNA expression profile of gastric adenocarcinoma (GAC). The variants of significantly dysregulated miRNA were genotyped in test (715 cases and 804 controls) and validation (940 cases and 1050 controls) subject sets. RESULTS: MiRNA microarray revealed that 12 miRNAs including miR-107 significantly dysregulated in GAC tissues. The sequencing of the promoter of miR-107 identified 3 SNPs (rs11185777, rs78591545, and rs2296616) with minor allele frequency (MAF)>5%. Analyzing their association with GAC risk and prognosis revealed that the C allele of rs2296616 (T>C) was significantly associated with the decreased risk of GAC among the test, validation and combined sets (TC/CC vs. TT, adjusted OR=0.39, 95% CI=0.31-0.49 for the combined set). However, the C allele was related to an unfavorable prognosis of Cardia GAC (CGAC) (adjusted HR=1.49, 95% CI=1.01-2.20). In vivo evidence showed that the individuals with the rs2296616C allele had lower miR-107 expression compared with the homozygous T allele carriers. CONCLUSION:miR-107 is dysregulated in GAC pathogenesis and the SNP rs2296616 may play a role in the process.