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MicroRNA networks in mouse lung organogenesis.

Dong J, Jiang G, Asmann YW, Tomaszek S, Jen J, Kislinger T, Wigle DA - PLoS ONE (2010)

Bottom Line: Of 1345 proteins analyzed, 55% appeared to be regulated in this manner with a direct correlation between miRNA and protein level, but without detectable change in mRNA levels.Systematic analysis of microRNA, mRNA, and protein levels over the time course of lung organogenesis demonstrates dynamic regulation and reveals 2 distinct patterns of miRNA-mRNA interaction.The translation of target proteins affected by miRNAs independent of changes in mRNA level appears to be a prominent mechanism of developmental regulation in lung organogenesis.

View Article: PubMed Central - PubMed

Affiliation: Division of General Thoracic Surgery, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, Minnesota, USA.

ABSTRACT

Background: MicroRNAs (miRNAs) are known to be important regulators of both organ development and tumorigenesis. MiRNA networks and their regulation of messenger RNA (mRNA) translation and protein expression in specific biological processes are poorly understood.

Methods: We explored the dynamic regulation of miRNAs in mouse lung organogenesis. Comprehensive miRNA and mRNA profiling was performed encompassing all recognized stages of lung development beginning at embryonic day 12 and continuing to adulthood. We analyzed the expression patterns of dynamically regulated miRNAs and mRNAs using a number of statistical and computational approaches, and in an integrated manner with protein levels from an existing mass-spectrometry derived protein database for lung development.

Results: In total, 117 statistically significant miRNAs were dynamically regulated during mouse lung organogenesis and clustered into distinct temporal expression patterns. 11,220 mRNA probes were also shown to be dynamically regulated and clustered into distinct temporal expression patterns, with 3 major patterns accounting for 75% of all probes. 3,067 direct miRNA-mRNA correlation pairs were identified involving 37 miRNAs. Two defined correlation patterns were observed upon integration with protein data: 1) increased levels of specific miRNAs directly correlating with downregulation of predicted mRNA targets; and 2) increased levels of specific miRNAs directly correlating with downregulation of translated target proteins without detectable changes in mRNA levels. Of 1345 proteins analyzed, 55% appeared to be regulated in this manner with a direct correlation between miRNA and protein level, but without detectable change in mRNA levels.

Conclusion: Systematic analysis of microRNA, mRNA, and protein levels over the time course of lung organogenesis demonstrates dynamic regulation and reveals 2 distinct patterns of miRNA-mRNA interaction. The translation of target proteins affected by miRNAs independent of changes in mRNA level appears to be a prominent mechanism of developmental regulation in lung organogenesis.

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Related in: MedlinePlus

Scatter plots of miRNA and mRNA data by Principle Component Analysis (PCA).(A) Expression array data for mRNA. (B) Expression array data for miRNA. Samples are colored by different mouse lung development time points. The same color represents the replicate samples.
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pone-0010854-g001: Scatter plots of miRNA and mRNA data by Principle Component Analysis (PCA).(A) Expression array data for mRNA. (B) Expression array data for miRNA. Samples are colored by different mouse lung development time points. The same color represents the replicate samples.

Mentions: In total, the expression values of 45,101 probes for mRNA profiling in 7 time points (2 samples in each time point) were obtained after normalization. The normalized expression values of 521 miRNAs in the same 7 time points (2 samples in each time point) were also obtained. The 3-D graphical visualization of the principal component (PCA) analysis for both mRNA and miRNA expression values from replicate samples in each time point have similar patterns (Figure 1).


MicroRNA networks in mouse lung organogenesis.

Dong J, Jiang G, Asmann YW, Tomaszek S, Jen J, Kislinger T, Wigle DA - PLoS ONE (2010)

Scatter plots of miRNA and mRNA data by Principle Component Analysis (PCA).(A) Expression array data for mRNA. (B) Expression array data for miRNA. Samples are colored by different mouse lung development time points. The same color represents the replicate samples.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2877109&req=5

pone-0010854-g001: Scatter plots of miRNA and mRNA data by Principle Component Analysis (PCA).(A) Expression array data for mRNA. (B) Expression array data for miRNA. Samples are colored by different mouse lung development time points. The same color represents the replicate samples.
Mentions: In total, the expression values of 45,101 probes for mRNA profiling in 7 time points (2 samples in each time point) were obtained after normalization. The normalized expression values of 521 miRNAs in the same 7 time points (2 samples in each time point) were also obtained. The 3-D graphical visualization of the principal component (PCA) analysis for both mRNA and miRNA expression values from replicate samples in each time point have similar patterns (Figure 1).

Bottom Line: Of 1345 proteins analyzed, 55% appeared to be regulated in this manner with a direct correlation between miRNA and protein level, but without detectable change in mRNA levels.Systematic analysis of microRNA, mRNA, and protein levels over the time course of lung organogenesis demonstrates dynamic regulation and reveals 2 distinct patterns of miRNA-mRNA interaction.The translation of target proteins affected by miRNAs independent of changes in mRNA level appears to be a prominent mechanism of developmental regulation in lung organogenesis.

View Article: PubMed Central - PubMed

Affiliation: Division of General Thoracic Surgery, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, Minnesota, USA.

ABSTRACT

Background: MicroRNAs (miRNAs) are known to be important regulators of both organ development and tumorigenesis. MiRNA networks and their regulation of messenger RNA (mRNA) translation and protein expression in specific biological processes are poorly understood.

Methods: We explored the dynamic regulation of miRNAs in mouse lung organogenesis. Comprehensive miRNA and mRNA profiling was performed encompassing all recognized stages of lung development beginning at embryonic day 12 and continuing to adulthood. We analyzed the expression patterns of dynamically regulated miRNAs and mRNAs using a number of statistical and computational approaches, and in an integrated manner with protein levels from an existing mass-spectrometry derived protein database for lung development.

Results: In total, 117 statistically significant miRNAs were dynamically regulated during mouse lung organogenesis and clustered into distinct temporal expression patterns. 11,220 mRNA probes were also shown to be dynamically regulated and clustered into distinct temporal expression patterns, with 3 major patterns accounting for 75% of all probes. 3,067 direct miRNA-mRNA correlation pairs were identified involving 37 miRNAs. Two defined correlation patterns were observed upon integration with protein data: 1) increased levels of specific miRNAs directly correlating with downregulation of predicted mRNA targets; and 2) increased levels of specific miRNAs directly correlating with downregulation of translated target proteins without detectable changes in mRNA levels. Of 1345 proteins analyzed, 55% appeared to be regulated in this manner with a direct correlation between miRNA and protein level, but without detectable change in mRNA levels.

Conclusion: Systematic analysis of microRNA, mRNA, and protein levels over the time course of lung organogenesis demonstrates dynamic regulation and reveals 2 distinct patterns of miRNA-mRNA interaction. The translation of target proteins affected by miRNAs independent of changes in mRNA level appears to be a prominent mechanism of developmental regulation in lung organogenesis.

Show MeSH
Related in: MedlinePlus