Abstract
Transcription factors (TFs) and microRNAs (miRNAs) are well-characterized trans-acting essential players in gene expression regulation. Growing evidence indicates that TFs and miRNAs can work cooperatively, and their dysregulation has been associated with many diseases including cancer. A unified picture of regulatory interactions of these regulators and their joint target genes would shed light on cancer studies. Although online resources developed to support probing of TF-gene and miRNA-gene interactions are available, online applications for miRNA-TF co-regulatory analysis, especially with a focus on cancers, are lacking. In light of this, we developed a web tool, namely CMTCN (freely available at http://www.cbportal.org/CMTCN), which constructs miRNA-TF co-regulatory networks and conducts comprehensive analyses within the context of particular cancer types. With its user-friendly provision of topological and functional analyses, CMTCN promises to be a reliable and indispensable web tool for biomedical studies.
Highlights
Gene expression regulation is a complex biological process involving various regulators across multiple levels
To better illustrate the functionality and utility of CMTCN, we studied the miRNA-transcription factors (TFs) co-regulation of two specific cancers, namely thyroid carcinoma (THCA) and ovarian cancer (OV)
CMTCN established a THCA-specific miRNA-TF co-regulatory network comprised of 391 nodes and 518 links, with 710 co-regulatory pairs, 7 TF-FFLs, 1 miRNAFFL, and 2 composite-FFLs
Summary
Gene expression regulation is a complex biological process involving various regulators across multiple levels. In gene expression regulation system, transcription factors (TFs) and microRNAs (miRNAs) have been recognized to play important roles at transcriptional level and post-transcriptional level respectively. Increasing evidence suggests that miRNAs and TFs are able to work together, mainly to buffer gene expression and/or adjust signaling (Bracken, Scott & Goodall, 2016). MiRNAs and TFs have been shown to regulate shared target genes in feed-forward-loops (FFLs) and co-regulating pairs (Zhang et al, 2013). MiRNA-TF FFLs and co-regulating pairs are major network motifs (i.e., genetic interconnection patterns that occur more often by chance in biological networks), serving as basic building blocks of a complex regulatory system
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