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Distinct sets of candidate genes control the development of breast cancer subtypes. The expression of many genes is regulated by the binding of their mRNAs with miRNAs. The prediction of miRNA associations and target genes is essential in studying of breast cancer. The MirTarget program defines the following features of binding miRNA to mRNA: the start of the initiation of miRNA binding to mRNA; the localization of miRNA binding sites in 5'-untranslated regions (5'UTR), coding domain sequences (CDS) and 3'-untranslated regions (3'UTR); the free energy of binding of all miRNA nucleotides with mRNA; the schemes of interactions of all miRNAs nucleotides with mRNAs. The mRNAs of many genes have clusters (miRNA binding sites with overlapping nucleotide sequences) located in 5'UTR, CDS, or 3'UTR. There are clusters in 5'UTR of mRNA EPOR, MAZ and NISCH candidate genes of HER2 subtype. There are four clusters in CDS of mRNA MAZ gene, and in 3'UTR of mRNA BRCA2 and CDK6 genes. Candidate genes of triple-negative subtype are targets for multiple miRNAs. In 5'UTR of mRNA СBL gene, there are 11 sites; the mRNA for MMP2 gene contains five sites; the mRNA of RAB5A gene contains two clusters each of three sites. In 3'UTR of mRNA SFN gene, there are two clusters, each of three sites, and one cluster of 21 sites. Candidate genes of luminal A and B subtypes are targets for miRNAs: there are 21 sites in 5'UTR of mRNA FOXA1 gene and mRNA HMGA2 gene contains 15 sites. There are clusters of five sites in CDS of mRNA ITGB1 gene and five sites in 3'UTR of mRNA SOX4 genes. Clusters of eight sites and ten sites are identified in 3'UTR of mRNA SMAD3 and TGFB1 genes, respectively. The organization of miRNA binding sites into clusters reduces the proportion of nucleotide binding sites in 5'UTR, CDS and 3'UTRs. This overlapping of miRNA binding sites creates a competition among miRNAs for the binding site. From 6,272 studied miRNAs only 29 miRNAs from miRBase and 88 novel miRNAs have binding sites in clusters of mRNA target genes of breast cancer.
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Schemes of miRNA interaction with mRNA of candidate genes of breast cancer triple-negative subtype