SNP Regulation of microRNA Expression and Subsequent Colon Cancer Risk.
SNP Regulation of microRNA Expression and Subsequent Colon Cancer Risk.
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DOI：
10.1371/journal.pone.0143894
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Slattery ML
中科院分区：
文献类型：
--
作者：
Mullany LE;Wolff RK;Herrick JS;Buas MF;Slattery ML
microRNA（miRNAs）调节信使RNA（mRNAs），因此与多种疾病（包括癌症）有关。miRNA通过miRNA 5'种子序列（~7-8个核苷酸）与mRNA 3' UTR的结合来调节mRNA;这些区域中的多态性具有改变miRNA-mRNA靶关联的潜力。已经提出miRNA基因以及miRNA靶基因中的SNP通过改变miRNA表达水平来影响癌症风险。通过文献鉴定miRNA-SNPs和miRNA-target基因-SNPs。我们使用了来自全基因组关联研究（GWAS）数据的SNP，这些数据与具有来自Agilent平台的结肠肿瘤和非肿瘤配对组织的miRNA表达数据的个体相匹配。这些样本用于评估327个miRNA-SNP对的SNP与miRNA表达水平之间的关联以及SNP与结肠癌的关联。在非肿瘤组织中表达的22种miRNA在基因型上存在显著差异，21种SNP与基因型间肿瘤/非肿瘤差异miRNA表达的改变相关。两种miRNA与非肿瘤和肿瘤/非肿瘤差异表达的SNP基因型相关。在41个与SNPs显著相关的miRNAs中，除7个外，其他所有miRNAs在结肠肿瘤组织中均显著差异表达。与miRNA表达水平显著相关的41个SNP中有2个与结肠癌风险相关：rs 8176318（BRCA 1），ORAA 1.31 95% CI 1.01，1.78，和rs 8905（PRKAR 1A），ORGG 2.31 95% CI 1.11，4.77。在文献中确定的327个SNP中，由于其对miRNA表达水平的潜在调节而被认为是重要的，12.5%与miRNA表达具有统计学显著相关性。然而，这些SNPs中只有两个与结肠癌显著相关。
MicroRNAs (miRNAs) regulate messenger RNAs (mRNAs) and as such have been implicated in a variety of diseases, including cancer. MiRNAs regulate mRNAs through binding of the miRNA 5’ seed sequence (~7–8 nucleotides) to the mRNA 3’ UTRs; polymorphisms in these regions have the potential to alter miRNA-mRNA target associations. SNPs in miRNA genes as well as miRNA-target genes have been proposed to influence cancer risk through altered miRNA expression levels. MiRNA-SNPs and miRNA-target gene-SNPs were identified through the literature. We used SNPs from Genome-Wide Association Study (GWAS) data that were matched to individuals with miRNA expression data generated from an Agilent platform for colon tumor and non-tumor paired tissues. These samples were used to evaluate 327 miRNA-SNP pairs for associations between SNPs and miRNA expression levels as well as for SNP associations with colon cancer. Twenty-two miRNAs expressed in non-tumor tissue were significantly different by genotype and 21 SNPs were associated with altered tumor/non-tumor differential miRNA expression across genotypes. Two miRNAs were associated with SNP genotype for both non-tumor and tumor/non-tumor differential expression. Of the 41 miRNAs significantly associated with SNPs all but seven were significantly differentially expressed in colon tumor tissue. Two of the 41 SNPs significantly associated with miRNA expression levels were associated with colon cancer risk: rs8176318 (BRCA1), ORAA 1.31 95% CI 1.01, 1.78, and rs8905 (PRKAR1A), ORGG 2.31 95% CI 1.11, 4.77. Of the 327 SNPs identified in the literature as being important because of their potential regulation of miRNA expression levels, 12.5% had statistically significantly associations with miRNA expression. However, only two of these SNPs were significantly associated with colon cancer.