Dissecting microregulation of a master regulatory network
- Equal contributors
1 Department of Computer Science, University of Cincinnati, Ohio, USA
2 Department of Biomedical Engineering, University of Cincinnati, Ohio, USA
3 Department of Pediatrics, University of Cincinnati College of Medicine, Ohio, USA
4 Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Ohio, USA
BMC Genomics 2008, 9:88 doi:10.1186/1471-2164-9-88Published: 23 February 2008
The master regulator p53 tumor-suppressor protein through coordination of several downstream target genes and upstream transcription factors controls many pathways important for tumor suppression. While it has been reported that some of the p53's functions are microRNA-mediated, it is not known as to how many other microRNAs might contribute to the p53-mediated tumorigenesis.
Here, we use bioinformatics-based integrative approach to identify and prioritize putative p53-regulated miRNAs, and unravel the miRNA-based microregulation of the p53 master regulatory network. Specifically, we identify putative microRNA regulators of a) transcription factors that are upstream or downstream to p53 and b) p53 interactants. The putative p53-miRs and their targets are prioritized using current knowledge of cancer biology and literature-reported cancer-miRNAs.
Our predicted p53-miRNA-gene networks strongly suggest that coordinated transcriptional and p53-miR mediated networks could be integral to tumorigenesis and the underlying processes and pathways.