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首页> 外文期刊>BMC Veterinary Research >Characterizing dynamic regulatory programs in mouse lung development and their potential association with tumourigenesis via miRNA-TF-mRNA circuits
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Characterizing dynamic regulatory programs in mouse lung development and their potential association with tumourigenesis via miRNA-TF-mRNA circuits

机译：通过miRNA-TF-mRNA电路表征小鼠肺发育中的动态调节程序及其与肿瘤发生的潜在关联

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BackgroundIn dynamic biological processes, genes, transcription factors(TF) and microRNAs(miRNAs) play vital regulation roles. Many researchers have focused on the transcription factors or miRNAs in transcriptional or post transcriptional stage, respectively. However, the transcriptional regulation and post transcriptional regulation is not isolated in the whole dynamic biological processes, there are few reserchers who have tried to consider the network composed by genes, miRNAs and TFs in this dynamic biological processes, especially in the mouse lung development. Moreover, it is widely acknowledged that cancer is a kind of developmental disorders, and some of pathways involved in tissue development might be also implicated in causing cancer. Although it has been found that many genes differentially expressed during mouse lung development are also differentially expressed in lung cancer, very little work has been reported to elucidate the combinational regulatory programs of such kind of associations.ResultsIn order to investigate the association of transcriptional and post-transcriptional regulating activities in the mouse lung development, we define the significant triple relations among miRNAs, TFs and mRNAs as circuits. From the lung development time course data GSE21053, we mine 142610 circuit candidates including 96 TFs, 129 miRNAs and 13403 genes. After removing genes with little variation along different time points, we finally find 64760 circuit candidates, containing 8299 genes, 50 TFs, and 118 miRNAs in total. Further analysis on the circuits shows that the circuits vary in different stages of the lung development and play different roles. By investigating the circuits in the context of lung specific genes, we identify out the regulatory combinations for lung specific genes, as well as for those lung non-specific genes. Moreover, we show that the lung non-specific genes involved circuits are functionally related to the lung development. Noticing that some tissue developmental systems may be involved in tumourigenesis, we also check the cancer genes involved circuits, trying to find out their regulatory program, which would be useful for the research of lung cancer.ConclusionsThe relevant transcriptional or post-transcriptional factors and their roles involved in the mouse lung development are both changed greatly in different stages. By investigating the cancer genes involved circuits, we can find miRNAs/TFs playing important roles in tumour progression. Therefore, the miRNA-TF-mRNA circuits can be used in wide translational biomedicine studies, and can provide potential drug targets towards the treatment of lung cancer.
机译：背景技术在动态生物过程中，基因，转录因子（TF）和微小RNA（miRNA）发挥着至关重要的调节作用。许多研究人员分别专注于转录阶段或转录后阶段的转录因子或miRNA。但是，转录调控和转录后调控在整个动态生物学过程中并不是孤立的，很少有研究者试图在这种动态生物学过程中考虑由基因，miRNA和TF组成的网络，特别是在小鼠肺部发育中。此外，众所周知，癌症是一种发育障碍，与组织发育有关的某些途径也可能与引起癌症有关。尽管已经发现在小鼠肺发育过程中许多差异表达的基因在肺癌中也有差异表达，但报道的工作很少能阐明这种关联的组合调控程序。结果为了研究转录与转录后的关联-转录调节活性在小鼠肺部发育中，我们将miRNA，TF和mRNA之间的重要三元关系定义为电路。从肺发育时程数据GSE21053中，我们挖掘了142610个候选电路，包括96个TF，129个miRNA和13403个基因。在去除了在不同时间点几乎没有变化的基因后，我们最终找到了64760个候选电路，总共包含8299个基因，50个TF和118个miRNA。对回路的进一步分析表明，回路在肺部发育的不同阶段发生变化，并发挥不同的作用。通过研究肺特异性基因的背景下的电路，我们找出了肺特异性基因以及那些肺非特异性基因的调控组合。此外，我们表明，涉及肺的非特异性基因与肺功能在功能上相关。注意到某些组织发育系统可能参与了肿瘤发生，我们还检查了涉及肿瘤的电路，试图找出其调控程序，这对肺癌的研究将是有用的。结论相关的转录或转录后因子及其小鼠肺发育中涉及的角色在不同阶段都发生了很大变化。通过研究涉及电路的癌症基因，我们可以发现在肿瘤进展中起重要作用的miRNA / TF。因此，miRNA-TF-mRNA电路可用于广泛的翻译生物医学研究中，并可为治疗肺癌提供潜在的药物靶标。

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