Nucleic Acids Research Advance Access originally published online on June 21, 2007
Nucleic Acids Research 2007 35(13):4535-4541; doi:10.1093/nar/gkm480
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Nucleic Acids Research, 2007, Vol. 35, No. 13 4535-4541
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Genomics |
Aberrant allele frequencies of the SNPs located in microRNA target sites are potentially associated with human cancers
1Health Sector, Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, Montréal, Québec, Canada, H4P 2R2 and 2Department of Medicine, McGill University, Montréal, Québec, Canada, H3G 1A4
*To whom correspondence should be addressed. Tel: +514 496 6318; Fax: +514 496 6319; Email: shi.shen{at}cnrc-nrc.gc.ca Correspondence may also be addressed to Zhenbao Yu. Tel: +514 496 6377; Fax: +514 496 6319; Email: zhenbao.yu{at}nrc.ca
Received October 3, 2006. Revised May 11, 2007. Accepted May 31, 2007.
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.
The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint First Authors.
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