The Pattern of microRNA Binding Site Distribution.
The Pattern of microRNA Binding Site Distribution.
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DOI：
10.3390/genes8110296
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发表时间：
2017-10-27
期刊：
影响因子：
3.5
通讯作者：
Wang D
中科院分区：
文献类型：
--
作者：
Zhang F;Wang D
微rna （miRNA或miR）通过其mRNA 3 ' -非翻译区（UTR）的靶位点调控人类基因组中至少60%的基因，并且在癌症中经常观察到miRNA表达调控和靶位点的缺陷。我们在此报告了miRNA靶点分布的系统分析。利用TargetScan数据库中进化上保守的miRNA结合位点（release 7.1），我们通过连接共享miRNA靶点的基因构建了miRNA共调控网络。该网络具有无处不在的小世界网络的特点。网络中的非枢纽基因——那些与少量基因共享miRNA目标位点的基因——倾向于与邻近基因形成小派系，而枢纽基因在其邻近基因中表现出高度的混杂性。此外，miRNA靶位分布极不均匀。在这些miRNAs中，分布集中在少数miRNAs上，因为它们的靶位点出现在异常多的基因中，即它们的靶基因数量非常多。基因之间的分布也遵循类似的模式；一小部分基因的mrna含有大量的miRNA结合位点。在数量上，这些模式符合P(K)∝K−α关系（P(K)）：含有K个靶基因或含有K个miRNA位点的基因的miRNA数量；α：正常数)，节点之间连接分布的数学描述，以及所谓的无标度网络（小世界网络的子集）的定义特征。值得注意的是，众所周知的肿瘤抑制miRNA （Let-7、miR-15/16、26、29、31、34、145、200、203-205、223和375）共同具有比预期更多的靶基因，众所周知的癌症基因含有比预期更多的miRNA结合位点。综上所述，miRNA靶点分布具有小世界网络的特点。讨论了利用这种模式更好地了解miRNA功能及其肿瘤学作用的潜力。
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−α relationship (P(K): the number of miRNAs with K target genes or genes with K miRNA sites; α: 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.
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DOI：
10.1073/pnas.231608898
发表时间：
2002-01-22
影响因子：
11.1
作者：
Berman, BP;Nibu, Y;Eisen, MB
通讯作者：
Eisen, MB
MicroRNA结合位点中的单核苷酸多态性：大肠癌的影响。
影响因子：
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作者：
Bhaumik P;Gopalakrishnan C;Kamaraj B;Purohit R
通讯作者：
Purohit R
影响因子：
56.9
作者：
Barabási, AL;Albert, R
通讯作者：
Albert, R
影响因子：
4.8
作者：
Bourguignon, Lilly Y. W.;Spevak, Christina C.;Gilad, Eli
通讯作者：
Gilad, Eli
影响因子：
10.7
作者：
Dermitzakis, ET;Clark, AG
通讯作者：
Clark, AG