miR-107启动子区的一种常见基因变异与胃腺癌易感性及生存率相关。
A common genetic variation in the promoter of miR-107 is associated with gastric adenocarcinoma susceptibility and survival.
作者信息
Wang Shizhi, Lv Chunye, Jin Hua, Xu Ming, Kang Meiyun, Chu Haiyan, Tong Na, Wu Dongmei, Zhu Haixia, Gong Weida, Zhao Qinghong, Tao Guoquan, Zhou Jianwei, Zhang Zhengdong, Wang Meilin
机构信息
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.
Department of General Surgery, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China.
出版信息
Mutat Res. 2014 Nov;769:35-41. doi: 10.1016/j.mrfmmm.2014.07.002. Epub 2014 Jul 16.
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.
背景
全球微小RNA（miRNA）表达谱已被广泛用于表征人类癌症。众所周知，miRNA中的基因变异可调节miRNA生物合成和疾病风险。
方法
采用全基因组miRNA微阵列评估胃腺癌（GAC）的miRNA表达谱。对显著失调的miRNA的变异在测试组（715例病例和804例对照）和验证组（940例病例和1050例对照）中进行基因分型。
结果
miRNA微阵列显示，包括miR-107在内的12种miRNA在GAC组织中显著失调。miR-107启动子测序鉴定出3个单核苷酸多态性（SNP）（rs11185777、rs78591545和rs2296616），其小等位基因频率（MAF）>5%。分析它们与GAC风险和预后的关联发现，rs2296616（T>C）的C等位基因在测试组、验证组和合并组中均与GAC风险降低显著相关（TC/CC与TT相比，合并组调整后的OR=0.39，95%CI=0.31-0.49）。然而，C等位基因与贲门胃腺癌（CGAC）的不良预后相关（调整后的HR=1.49，95%CI=1.01-2.20）。体内证据表明，与纯合T等位基因携带者相比，携带rs2296616C等位基因的个体miR-107表达较低。
结论
miR-107在GAC发病机制中失调，SNP rs2296616可能在此过程中发挥作用。
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