Transcription factor and microRNA co-regulatory loops: important regulatory motifs in biological processes and diseases

Abstract

Transcription factors (TFs) and microRNAs (miRNAs) can jointly regulate target gene expression in the forms of feed-forward loops (FFLs) or feedback loops (FBLs). These regulatory loops serve as important motifs in gene regulatory networks and play critical roles in multiple biological processes and different diseases. Major progress has been made in bioinformatics and experimental study for the TF and miRNA co-regulation in recent years. To further speed up its identification and functional study, it is indispensable to make a comprehensive review. In this article, we summarize the types of FFLs and FBLs and their identified methods. Then, we review the behaviors and functions for the experimentally identified loops according to biological processes and diseases. Future improvements and challenges are also discussed, which includes more powerful bioinformatics approaches and high-throughput technologies in TF and miRNA target prediction, and the integration of networks of multiple levels.

The pivotal role of small non-coding RNAs in the regulation of seed development

“…Some TFs and their targets are well-known components of many network motifs (Tyson and Novák 2010). More recently, miRNAs have also been integrated as components of these circuits, acting either as targets or repressors of TFs (Zhang et al 2015b). Given the central role of TFs in most regulatory networks and their high representation among plant miRNA target genes, miRNAs have also attracted attention in the context of the systems biology field.…”

Molecular dysfunctions in acute myeloid leukemia revealed by integrated analysis of microRNA and transcription factor

“…By integrating diverse data sources, systems biology approaches provide a powerful tool for exploring the interactions and searching for key regulators between disease candidate genes on the network level, which may help to explain key aspects of disease pathogenesis and leading to new candidates for the putative therapeutic targets (48). As major regulators of gene expression, miRNAs and TFs can function as tumor suppressors or oncogenes in a cooperative way to control gene expression, which triggering global alterations of genetic programs are involved in cell proliferation, differentiation, development and apoptosis in multiple human cancers (18). Ye et al (49) constructed a miRNA-TF regulatory network in T-cell acute lymphoblastic leukemia and demonstrated the roles of miR-19 (hub miRNA) and CYLD (hub gene) in the T-cell leukemogenesis.…”

“…NFKB1 and Myc transcriptionally suppressed miR-29b-3p expression by binding to its promoter, and MYC was confirmed as a transcriptional repressor of miR-15a-5p, which were in accord with the same TF→miRNA regulatory relationships in our network (34,35). As key regulators of gene expression, miRNAs and TFs may reciprocally regulate each other to form FBLs, or co-regulate the expression of the same targets to form FFLs (18). In our miRNA-TF regulatory network, we identified 13 FBL and 1156 FFL motifs, reflecting the tight relationships between miRNAs and TFs in the network.…”

“…TFs are trans-acting protein factors that control the transcription of target genes through specifically binding to the TFBS located within promoter region of target genes (18). As two major types of regulators of gene expression, TFs and miRNAs are able to tightly coordinate to ensure precise and accurate gene expression.…”

“…As two major types of regulators of gene expression, TFs and miRNAs are able to tightly coordinate to ensure precise and accurate gene expression. TF and miRNA may reciprocally regulate one another and both can regulate the expression of target genes in a combinatorial manner (18,19). It has been reported that miR-223 and transcription factor E2F1 regulate each other to form negative feedback loop in AML (20).…”