Characterizing dynamic regulatory programs in mouse lung development and their potential association with tumourigenesis via miRNA-TF-mRNA circuits

Abstract

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.

Integrated aqueous humor ceRNA and miRNA–TF–mRNA network analysis reveals potential molecular mechanisms governing primary open-angle glaucoma pathogenesis

“…In eukaryotes, both TFs and miRNAs serve as primary regulators of gene expression, with TFs serving to directly control DNA transcription[ 12 , 13 ] and miRNAs functioning by binding to conserved MREs to disrupt target mRNA translation at the posttranscriptional level. [ 14 , 15 ] In previous analyses, miRNAs have been shown to control anterior chamber shape, IOP, and RGC apoptosis via the regulation of specific target genes.…”

Integrated aqueous humor ceRNA and miRNA-TF-mRNA network analysis reveals potential molecular mechanisms governing primary open-angle glaucoma pathogenesis

“…In eukaryotes, both TFs and miRNAs serve as primary regulators of gene expression, with TFs serving to directly control DNA transcription [13,14] and miRNAs functioning by binding to conserved MREs to disrupt target mRNA translation at the post-transcriptional level [15,16,17,18]. In prior analyses, miRNAs have been shown to control anterior chamber shape, IOP, and RGC apoptosis via the regulation of specific target genes [19].…”

Systems biology study of transcriptional and post-transcriptional co-regulatory network sheds light on key regulators involved in important biological processes in Citrus sinensis

“…Cantini et al (2015) proposed a multi-network-based strategy to integrate different layers of genomic information including transcription factor cotargeting, microRNA co-targeting, protein-protein interaction and gene co-expression networks in order to find new candidate driver cancer genes in four cancer types. Liu et al (2013) defined the significant triple relations among miRNAs, TFs and mRNAs from mouse lung development time course data. This study reveals that circuits vary in different stages of development and play different roles in biological pathways.…”