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2017 ; 8
(11
): ä Nephropedia Template TP
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The Pattern of microRNA Binding Site Distribution
#MMPMID29077021
Zhang F
; Wang D
Genes (Basel)
2017[Oct]; 8
(11
): ä PMID29077021
show ga
Micro-RNA (miRNA or miR) regulates at least 60% of the genes in the human genome
through their target sites at mRNA 3'-untranslated regions (UTR), and defects in
miRNA expression regulation and target sites are frequently observed in cancers.
We report here a systematic analysis of the distribution of miRNA target sites.
Using the evolutionarily conserved miRNA binding sites in the TargetScan database
(release 7.1), we constructed a miRNA co-regulation network by connecting genes
sharing common miRNA target sites. The network possesses characteristics of the
ubiquitous small-world network. Non-hub genes in the network-those sharing miRNA
target sites with small numbers of genes-tend to form small cliques with their
neighboring genes, while hub genes exhibit high levels of promiscuousness in
their neighboring genes. Additionally, miRNA target site distribution is
extremely uneven. Among the miRNAs, the distribution concentrates on a small
number of miRNAs, in that their target sites occur in an extraordinarily large
number of genes, that is, they have large numbers of target genes. The
distribution across the genes follows a similar pattern; the mRNAs of a small
proportion of the genes contain extraordinarily large numbers of miRNA binding
sites. Quantitatively, the patterns fit into the P((K)) ? K(-)(?) relationship
(P((K)): the number of miRNAs with K target genes or genes with K miRNA sites; ?:
a positive constant), the mathematical description of connection distribution
among the nodes and a defining characteristic of the so-called scale-free
networks-a subset of small-world networks. Notably, well-known tumor-suppressive
miRNAs (Let-7, miR-15/16, 26, 29, 31, 34, 145, 200, 203-205, 223, and 375)
collectively have more than expected target genes, and well-known cancer genes
contain more than expected miRNA binding sites. In summary, miRNA target site
distribution exhibits characteristics of the small-world network. The potential
to use this pattern to better understand miRNA function and their oncological
roles is discussed.