Aberrant allele frequencies of the SNPs located in microRNA target sites are potentially associated with human cancers.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Yu, Z; Li, Z; Jolicoeur, N; Zhang, L; Fortin, Y; Wang, E; Wu, M; Shen, S-H

Published Date

  • 2007

Published In

Volume / Issue

  • 35 / 13

Start / End Page

  • 4535 - 4541

PubMed ID

  • 17584784

Pubmed Central ID

  • 17584784

Electronic International Standard Serial Number (EISSN)

  • 1362-4962

Digital Object Identifier (DOI)

  • 10.1093/nar/gkm480

Language

  • eng

Conference Location

  • England