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Dissecting microregulation of a master regulatory network.

Sinha AU, Kaimal V, Chen J, Jegga AG - BMC Genomics (2008)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics, University of Cincinnati College of Medicine, Ohio, USA. sinhaam@ececs.uc.edu

ABSTRACT

Background: 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.

Results: 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.

Conclusion: 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.

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Related in: MedlinePlus

Heat map representation of p53-miRs and their target genes relative to the p53 network. Panels A, B, C and D depict p53-miRs exclusively targeting p53 upstream activators, upstream repressors, downstream activators and downstream repressors respectively along with their predicted target transcription factors.
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Figure 3: Heat map representation of p53-miRs and their target genes relative to the p53 network. Panels A, B, C and D depict p53-miRs exclusively targeting p53 upstream activators, upstream repressors, downstream activators and downstream repressors respectively along with their predicted target transcription factors.

Mentions: Based on MAMI predictions, a total of 242 different miRNAs suppress p53 regulators or targets. Of these, 115 (~48%) are p53-miRs (Figure 2A). Some of the p53-miRs (32/143; Figure 2B) are found to exclusively target p53 upstream activators (13/143 p53-miRs; Figure 3A) or repressors (5/143; Figure 3B) or downstream activators (9/143; Figure 3C) or repressors (5/143; Figure 3D). Interestingly, many of these miRNAs have been reported as differentially expressed in various cancerous tissues or cell lines (see last column in Table 1).


Dissecting microregulation of a master regulatory network.

Sinha AU, Kaimal V, Chen J, Jegga AG - BMC Genomics (2008)

Heat map representation of p53-miRs and their target genes relative to the p53 network. Panels A, B, C and D depict p53-miRs exclusively targeting p53 upstream activators, upstream repressors, downstream activators and downstream repressors respectively along with their predicted target transcription factors.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2289817&req=5

Figure 3: Heat map representation of p53-miRs and their target genes relative to the p53 network. Panels A, B, C and D depict p53-miRs exclusively targeting p53 upstream activators, upstream repressors, downstream activators and downstream repressors respectively along with their predicted target transcription factors.
Mentions: Based on MAMI predictions, a total of 242 different miRNAs suppress p53 regulators or targets. Of these, 115 (~48%) are p53-miRs (Figure 2A). Some of the p53-miRs (32/143; Figure 2B) are found to exclusively target p53 upstream activators (13/143 p53-miRs; Figure 3A) or repressors (5/143; Figure 3B) or downstream activators (9/143; Figure 3C) or repressors (5/143; Figure 3D). Interestingly, many of these miRNAs have been reported as differentially expressed in various cancerous tissues or cell lines (see last column in Table 1).

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics, University of Cincinnati College of Medicine, Ohio, USA. sinhaam@ececs.uc.edu

ABSTRACT

Background: 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.

Results: 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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus