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

Nucleic Acids Res. 2007;35(13):4535-41. doi: 10.1093/nar/gkm480. Epub 2007 Jun 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics*
  • 3' Untranslated Regions / metabolism
  • Binding Sites
  • Databases, Nucleic Acid
  • Gene Expression Regulation
  • Gene Frequency*
  • Gene Library
  • Genome, Human
  • Humans
  • MicroRNAs / metabolism*
  • Neoplasms / genetics*
  • Polymorphism, Single Nucleotide*
  • RNA, Messenger / metabolism


  • 3' Untranslated Regions
  • MicroRNAs
  • RNA, Messenger