Institute of Biomedical Informatics, Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei, Taiwan.
BMC Bioinformatics. 2011 Feb 15;12 Suppl 1(Suppl 1):S41. doi: 10.1186/1471-2105-12-S1-S41.
MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression at the post-transcriptional level. Recent studies have suggested that miRNAs and transcription factors are primary metazoan gene regulators; however, the crosstalk between them still remains unclear.
We proposed a novel model utilizing functional annotation information to identify significant coregulation between transcriptional and post-transcriptional layers. Based on this model, function-enriched coregulation relationships were discovered and combined into different kinds of functional coregulation networks.
We found that miRNAs may engage in a wider diversity of biological processes by coordinating with transcription factors, and this kind of cross-layer coregulation may have higher specificity than intra-layer coregulation. In addition, the coregulation networks reveal several types of network motifs, including feed-forward loops and massive upstream crosstalk. Finally, the expression patterns of these coregulation pairs in normal and tumour tissues were analyzed. Different coregulation types show unique expression correlation trends. More importantly, the disruption of coregulation may be associated with cancers.
Our findings elucidate the combinatorial and cooperative properties of transcription factors and miRNAs regulation, and we proposes that the coordinated regulation may play an important role in many biological processes.
微小 RNA（miRNAs）是一种小 RNA 分子，可在转录后水平调节基因表达。最近的研究表明，miRNAs 和转录因子是真核生物的主要基因调控因子，但它们之间的串扰仍然不清楚。
我们提出了一种利用功能注释信息来识别转录和转录后层之间显著核心调控的新模型。基于该模型，发现了功能丰富的核心调控关系，并将其组合成不同类型的功能核心调控网络。
我们发现，miRNAs 通过与转录因子的协调，可能参与更广泛的生物过程，并且这种跨层核心调控比层内核心调控具有更高的特异性。此外，核心调控网络揭示了几种类型的网络基元，包括前馈环和大量上游串扰。最后，分析了这些核心调控对在正常和肿瘤组织中的表达模式。不同的核心调控类型表现出独特的表达相关趋势。更重要的是，核心调控的破坏可能与癌症有关。
我们的研究结果阐明了转录因子和 miRNAs 调控的组合和协同特性，我们提出协调调控可能在许多生物学过程中发挥重要作用。
