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Correlation of microRNA levels during hypoxia with predicted target mRNAs through genome-wide microarray analysis.

Guimbellot JS, Erickson SW, Mehta T, Wen H, Page GP, Sorscher EJ, Hong JS - BMC Med Genomics (2009)

Bottom Line: To date, few studies have investigated an environmental perturbation for effects on genome-wide miRNA levels, or their consequent influence on mRNA output.Target prediction programs and expression profiling techniques do not yet adequately represent the complexity of miRNA-mediated gene repression, and new methods may be required to better elucidate these pathways.Our data suggest the physiologic impact of miRNAs on cellular transcription results from a multifaceted network of miRNA and mRNA relationships, working together in an interconnected system and in context of hundreds of RNA species.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA. jsguimbellot@uasom.uab.edu

ABSTRACT

Background: Low levels of oxygen in tissues, seen in situations such as chronic lung disease, necrotic tumors, and high altitude exposures, initiate a signaling pathway that results in active transcription of genes possessing a hypoxia response element (HRE). The aim of this study was to investigate whether a change in miRNA expression following hypoxia could account for changes in the cellular transcriptome based on currently available miRNA target prediction tools.

Methods: To identify changes induced by hypoxia, we conducted mRNA- and miRNA-array-based experiments in HT29 cells, and performed comparative analysis of the resulting data sets based on multiple target prediction algorithms. To date, few studies have investigated an environmental perturbation for effects on genome-wide miRNA levels, or their consequent influence on mRNA output.

Results: Comparison of miRNAs with predicted mRNA targets indicated a lower level of concordance than expected. We did, however, find preliminary evidence of combinatorial regulation of mRNA expression by miRNA.

Conclusion: Target prediction programs and expression profiling techniques do not yet adequately represent the complexity of miRNA-mediated gene repression, and new methods may be required to better elucidate these pathways. Our data suggest the physiologic impact of miRNAs on cellular transcription results from a multifaceted network of miRNA and mRNA relationships, working together in an interconnected system and in context of hundreds of RNA species. The methods described here for comparative analysis of cellular miRNA and mRNA will be useful for understanding genome wide regulatory responsiveness and refining miRNA predictive algorithms.

No MeSH data available.


Related in: MedlinePlus

Correlation of miRNAs with at least 3 target sites in miRanda-predicted target mRNA. Same as Figure 3, except that probes identified as targets of a miRNA are required to have at least three target sites in the 3'UTR region according to the miRanda(microrna.org) target prediction software. Arrows indicate deviation from the reference graph.
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Figure 7: Correlation of miRNAs with at least 3 target sites in miRanda-predicted target mRNA. Same as Figure 3, except that probes identified as targets of a miRNA are required to have at least three target sites in the 3'UTR region according to the miRanda(microrna.org) target prediction software. Arrows indicate deviation from the reference graph.

Mentions: Similar comparisons were made for mRNAs containing at least three target sites within each 3'UTR for the same miRNA (Figure 7). As in Figure 3, the 13 most significant differentially expressed miRNAs (Figure 7a) and 20 randomly selected, non-significant miRNAs (Figure 7b) were investigated. Certain miRNAs did exhibit some relationship with their predicted targets (indicated by arrows); however, miRNAs without statistically significant differential expression also demonstrated a roughly comparable relationship (arrows, Figures 7c and 7d), suggesting that this observation occurred by chance.


Correlation of microRNA levels during hypoxia with predicted target mRNAs through genome-wide microarray analysis.

Guimbellot JS, Erickson SW, Mehta T, Wen H, Page GP, Sorscher EJ, Hong JS - BMC Med Genomics (2009)

Correlation of miRNAs with at least 3 target sites in miRanda-predicted target mRNA. Same as Figure 3, except that probes identified as targets of a miRNA are required to have at least three target sites in the 3'UTR region according to the miRanda(microrna.org) target prediction software. Arrows indicate deviation from the reference graph.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2667434&req=5

Figure 7: Correlation of miRNAs with at least 3 target sites in miRanda-predicted target mRNA. Same as Figure 3, except that probes identified as targets of a miRNA are required to have at least three target sites in the 3'UTR region according to the miRanda(microrna.org) target prediction software. Arrows indicate deviation from the reference graph.
Mentions: Similar comparisons were made for mRNAs containing at least three target sites within each 3'UTR for the same miRNA (Figure 7). As in Figure 3, the 13 most significant differentially expressed miRNAs (Figure 7a) and 20 randomly selected, non-significant miRNAs (Figure 7b) were investigated. Certain miRNAs did exhibit some relationship with their predicted targets (indicated by arrows); however, miRNAs without statistically significant differential expression also demonstrated a roughly comparable relationship (arrows, Figures 7c and 7d), suggesting that this observation occurred by chance.

Bottom Line: To date, few studies have investigated an environmental perturbation for effects on genome-wide miRNA levels, or their consequent influence on mRNA output.Target prediction programs and expression profiling techniques do not yet adequately represent the complexity of miRNA-mediated gene repression, and new methods may be required to better elucidate these pathways.Our data suggest the physiologic impact of miRNAs on cellular transcription results from a multifaceted network of miRNA and mRNA relationships, working together in an interconnected system and in context of hundreds of RNA species.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA. jsguimbellot@uasom.uab.edu

ABSTRACT

Background: Low levels of oxygen in tissues, seen in situations such as chronic lung disease, necrotic tumors, and high altitude exposures, initiate a signaling pathway that results in active transcription of genes possessing a hypoxia response element (HRE). The aim of this study was to investigate whether a change in miRNA expression following hypoxia could account for changes in the cellular transcriptome based on currently available miRNA target prediction tools.

Methods: To identify changes induced by hypoxia, we conducted mRNA- and miRNA-array-based experiments in HT29 cells, and performed comparative analysis of the resulting data sets based on multiple target prediction algorithms. To date, few studies have investigated an environmental perturbation for effects on genome-wide miRNA levels, or their consequent influence on mRNA output.

Results: Comparison of miRNAs with predicted mRNA targets indicated a lower level of concordance than expected. We did, however, find preliminary evidence of combinatorial regulation of mRNA expression by miRNA.

Conclusion: Target prediction programs and expression profiling techniques do not yet adequately represent the complexity of miRNA-mediated gene repression, and new methods may be required to better elucidate these pathways. Our data suggest the physiologic impact of miRNAs on cellular transcription results from a multifaceted network of miRNA and mRNA relationships, working together in an interconnected system and in context of hundreds of RNA species. The methods described here for comparative analysis of cellular miRNA and mRNA will be useful for understanding genome wide regulatory responsiveness and refining miRNA predictive algorithms.

No MeSH data available.


Related in: MedlinePlus