title: Aberrant allele frequencies of the SNPs located in microRNA target sites are potentially associated with human cancers.
abstract: 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.
authors.affiliation: Health Sector, Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, Montréal, Québec, Canada. zhenbao.yu@nrc.ca
authors.forename: Zhenbao
authors.initials: Z
authors.lastname: Yu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Normand
authors.initials: N
authors.lastname: Jolicoeur
authors.forename: Linhua
authors.initials: L
authors.lastname: Zhang
authors.forename: Yves
authors.initials: Y
authors.lastname: Fortin
authors.forename: Edwin
authors.initials: E
authors.lastname: Wang
authors.forename: Meiqun
authors.initials: M
authors.lastname: Wu
authors.forename: Shi-Hsiang
authors.initials: SH
authors.lastname: Shen
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D030561:Databases, Nucleic Acid; D005786:Gene Expression Regulation; D005787:Gene Frequency; D015723:Gene Library; D015894:Genome, Human; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D012333:RNA, Messenger