Abstract
Gene regulation is viewed as a complex process where regulatory elements and their targets form highly complex network interactions thus affecting normal biological physiology and also disease-initiation and progress. Transcription factors (TF) and microRNA (miRNA) are fundamental transcriptional and post-transcriptional regulators of the gene expression controlling important biological processes. In recent years, many high throughput studies revealed that the complex regulatory interactions are mediated by the complex interplay between miRNA and TF regulating a Target Gene (TG) in conjunction. miRNAs and TFs are also known to regulate each other. This complex coregulatory mechanism may be represented in the form of miRNA:TF:TG coregulatory network. This network can be used to identify several small recurring subgraphs known as regulatory-circuits. One of these regulatory-circuits also called the Feed-Forward Loops (FFLs) is a three-node pattern which is composed of a miRNA and a TF, one of which regulates the other and both jointly regulate a TG. These regulatory-circuits have proven useful in elucidating the complex interplay of gene regulation during many physiological and pathological conditions.
Human.miRFFL.DB is a comprehensive integrated resource for human miRNA:TF:TG coregulatory directed networks and their associated regulatory-circuits. In-house scripts based on the graph theory principle have been used to identify both types of FFL motifs i.e. miRNA-FFL and TF-FFL. The database additionally provides an interactive visualization of the coregulatory networks and associated FFLs. Human.miRFFL.DB can be used as a comprehensive ready reference for human miRNA:TF:TG coregulatory networks and associated FFLs for decrypting complex cellular interactions of these regulatory biomolecules. Human.miRFFL.DB is available online at http://mirffldb.in/human/
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Highlights
microRNA (miRNA) and Transcriptional Factors (TFs) are two important regulatory biomolecules and a complex interplay between the two control a Target Gene (TG).
The tripartite regulatory-circuits of TF, miRNA regulating a common TG is known as regulatory-circuit.
Regulatory-circuits are extensively used to uncover underlying regulatory mechanisms in many physiological, pathophysiological and pathological conditions.
Human.miRFFL.DB offers a comprehensive repository of 2,596 human miRNA:TF:TG coregulatory networks and ~ associated regulatory circuits.
Human.miRFFL.DB also provides an interactive visualization of coregulatory networks and the network motifs.
The interplay between miRNAs, TFs and TGs help to get new mechanistic insights into complex molecular and cellular regulatory processes during complex multifactorial diseases.
New data has been added to the database. The front-end of the database is updated to make it's GUI more user-friendly and impressive. Figure 1 has changed. The URL of the database is changed. Aspects on Eutherian comparison are added. Supplementary data has changed.
Abbreviations
- TF
- Transcription factor
- TG
- Target Gene
- FFL
- Feed Forward Loop
- MTI
- miRNA-Target Interaction
- coTF
- Co Transcription Factor