Tran Dang Hung, Satou Kenji, Ho Tu Bao, Pham Tho Hoan
School of Knowledge Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292, Japan; Hanoi National University of Education, 136 Xuanthuy, Caugiay, Hanoi, Vietnam.
Bioinformation. 2010 Feb 28;4(8):371-7. doi: 10.6026/97320630004371.
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. They play an important role in several biological processes such as cell development and differentiation. Similar to transcription factors (TFs), miRNAs regulate gene expression in a combinatorial fashion, i.e., an individual miRNA can regulate multiple genes, and an individual gene can be regulated by multiple miRNAs. The functions of TFs in biological regulatory networks have been well explored. And, recently, a few studies have explored miRNA functions in the context of gene regulation networks. However, how TFs and miRNAs function together in the gene regulatory network has not yet been examined. In this paper, we propose a new computational method to discover the gene regulatory modules that consist of miRNAs, TFs, and genes regulated by them. We analyzed the regulatory associations among the sets of predicted miRNAs and sets of TFs on the sets of genes regulated by them in the human genome. We found 182 gene regulatory modules of combinatorial regulation by miRNAs and TFs (miR-TF modules). By validating these modules with the Gene Ontology (GO) and the literature, it was found that our method allows us to detect functionally-correlated gene regulatory modules involved in specific biological processes. Moreover, our miR-TF modules provide a global view of coordinated regulation of target genes by miRNAs and TFs.
微小RNA（miRNA）是一类小的非编码RNA，它们在转录后水平调控基因表达。它们在细胞发育和分化等多个生物学过程中发挥重要作用。与转录因子（TF）类似，miRNA以组合方式调控基因表达，即单个miRNA可以调控多个基因，单个基因也可以被多个miRNA调控。转录因子在生物调控网络中的功能已得到充分研究。最近，一些研究在基因调控网络的背景下探索了miRNA的功能。然而，转录因子和miRNA在基因调控网络中如何共同发挥作用尚未得到研究。在本文中，我们提出了一种新的计算方法，用于发现由miRNA、转录因子及其调控的基因组成的基因调控模块。我们分析了人类基因组中预测的miRNA集合与转录因子集合在它们所调控的基因集合上的调控关联。我们发现了182个由miRNA和转录因子组合调控的基因调控模块（miR-TF模块）。通过用基因本体论（GO）和文献对这些模块进行验证，发现我们的方法能够检测参与特定生物学过程的功能相关基因调控模块。此外，我们的miR-TF模块提供了miRNA和转录因子对靶基因协同调控的全局视图。
