Aberrant allele frequencies of the SNPs located in microRNA target sites are potentially associated with human cancers.
Aberrant allele frequencies of the SNPs located in microRNA target sites are potentially associated with human cancers.
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DOI：
10.1093/nar/gkm480
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发表时间：
2007
影响因子：
14.9
通讯作者：
Shen SH
中科院分区：
文献类型：
--
作者：
Yu Z;Li Z;Jolicoeur N;Zhang L;Fortin Y;Wang E;Wu M;Shen SH
MicroRNA (miRNA) 是一类非编码小 RNA，通过与目标 mRNA 的 3' 末端非翻译区 (3'-UTR) 碱基配对来调节基因表达，从而导致 mRNA 裂解或翻译抑制。位于 miRNA 结合位点的单核苷酸多态性 (SNP)（miRNA 结合 SNP）可能会影响 miRNA 靶标的表达，并可能导致人类对常见疾病的易感性。我们在此对位于各种人类基因 3'-UTR 的 miRNA 结合位点的 SNP 进行了全基因组分析。我们发现，就 miRNA 结合“种子”序列和整个 3'-UTR 序列之间的 SNP 分布而言，miRNA 结合 SNP 是负选择的。此外，我们通过挖掘 EST 数据库全面定义了癌症与正常组织中每个 miRNA 结合 SNP 的表达。有趣的是，我们发现一些 miRNA 结合 SNP 在人类癌症 EST 文库和 dbSNP 数据库之间表现出显着不同的等位基因频率。更重要的是，使用人类癌症样本对照 dbSNP 数据库进行病例对照关联研究，我们发现 12 个 miRNA 结合 SNP 确实在人类癌症中显示出异常的等位基因频率。因此，位于 miRNA 结合位点的 SNP 会影响 miRNA 靶标的表达和功能，并可能与癌症相关。
MicroRNAs (miRNAs) are a class of noncoding small RNAs that regulate gene expression by base pairing with target mRNAs at the 3′-terminal untranslated regions (3′-UTRs), leading to mRNA cleavage or translational repression. Single-nucleotide polymorphisms (SNPs) located at miRNA-binding sites (miRNA-binding SNPs) are likely to affect the expression of the miRNA target and may contribute to the susceptibility of humans to common diseases. We herein performed a genome-wide analysis of SNPs located in the miRNA-binding sites of the 3′-UTR of various human genes. We found that miRNA-binding SNPs are negatively selected in respect to SNP distribution between the miRNA-binding ‘seed’ sequence and the entire 3′-UTR sequence. Furthermore, we comprehensively defined the expression of each miRNA-binding SNP in cancers versus normal tissues through mining EST databases. Interestingly, we found that some miRNA-binding SNPs exhibit significant different allele frequencies between the human cancer EST libraries and the dbSNP database. More importantly, using human cancer specimens against the dbSNP database for case-control association studies, we found that twelve miRNA-binding SNPs indeed display an aberrant allele frequency in human cancers. Hence, SNPs located in miRNA-binding sites affect miRNA target expression and function, and are potentially associated with cancers.
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