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Discovering dysfunction of multiple microRNAs cooperation in disease by a conserved microRNA co-expression network.

Xiao Y, Xu C, Guan J, Ping Y, Fan H, Li Y, Zhao H, Li X - PLoS ONE (2012)

Bottom Line: Our analysis reveals that many miRNAs in the same sub-network are associated with the same diseases.Our results imply that multiple co-expressed miRNAs can cooperatively regulate a given biological process by targeting common components of that process, and the pathogenesis of disease may be associated with the abnormality of multiple functionally cooperative miRNAs rather than individual miRNAs.In addition, many of these co-expression relationships provide strong evidence for the involvement of new miRNAs in important biological processes, such as apoptosis, differentiation and cell cycle, indicating their potential disease links.

View Article: PubMed Central - PubMed

Affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China.

ABSTRACT
MicroRNAs, a new class of key regulators of gene expression, have been shown to be involved in diverse biological processes and linked to many human diseases. To elucidate miRNA function from a global perspective, we constructed a conserved miRNA co-expression network by integrating multiple human and mouse miRNA expression data. We found that these conserved co-expressed miRNA pairs tend to reside in close genomic proximity, belong to common families, share common transcription factors, and regulate common biological processes by targeting common components of those processes based on miRNA targets and miRNA knockout/transfection expression data, suggesting their strong functional associations. We also identified several co-expressed miRNA sub-networks. Our analysis reveals that many miRNAs in the same sub-network are associated with the same diseases. By mapping known disease miRNAs to the network, we identified three cancer-related miRNA sub-networks. Functional analyses based on targets and miRNA knockout/transfection data consistently show that these sub-networks are significantly involved in cancer-related biological processes, such as apoptosis and cell cycle. Our results imply that multiple co-expressed miRNAs can cooperatively regulate a given biological process by targeting common components of that process, and the pathogenesis of disease may be associated with the abnormality of multiple functionally cooperative miRNAs rather than individual miRNAs. In addition, many of these co-expression relationships provide strong evidence for the involvement of new miRNAs in important biological processes, such as apoptosis, differentiation and cell cycle, indicating their potential disease links.

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Evaluation of the conserved co-expression relationships.(A) Pie charts of miRNA expression data from human (top) and mouse (bottom) included in the analysis. Colors represent different tissues. (B) Probability density of the number of co-expression links identified through the permutation of orthologous miRNAs. The permutation experiment was repeated 100 times. (C) ROC curves used to quantify the significant of these relationships using a PCR-based miRNA expression data (GSE23024).
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pone-0032201-g001: Evaluation of the conserved co-expression relationships.(A) Pie charts of miRNA expression data from human (top) and mouse (bottom) included in the analysis. Colors represent different tissues. (B) Probability density of the number of co-expression links identified through the permutation of orthologous miRNAs. The permutation experiment was repeated 100 times. (C) ROC curves used to quantify the significant of these relationships using a PCR-based miRNA expression data (GSE23024).

Mentions: We collected 16 human and 8 mouse miRNA expression data sets respectively including 611 and 107 samples (Figure 1A). All expression data sets were generated using Agilent arrays. After normalization and probes mapping, 702 and 490 mature miRNAs were consistently present in human and mouse miRNA expression data sets, respectively. To identify miRNAs that are co-expressed across human and mouse, we identified 285 human-mouse orthologous miRNAs by all-against-all alignment of precursor miRNA (pre-miRNA) sequences with 11 bp flanking regions. Because all expression data sets used in this study are specific for mature miRNAs, we then linked mature miRNAs in human with their corresponding mature miRNAs in mouse according to these 285 orthologous miRNAs. Finally, 341 human-mouse orthologous mature miRNAs were identified. Of these, 253 with both members having expression measurements were used in the following analysis (Table S1).


Discovering dysfunction of multiple microRNAs cooperation in disease by a conserved microRNA co-expression network.

Xiao Y, Xu C, Guan J, Ping Y, Fan H, Li Y, Zhao H, Li X - PLoS ONE (2012)

Evaluation of the conserved co-expression relationships.(A) Pie charts of miRNA expression data from human (top) and mouse (bottom) included in the analysis. Colors represent different tissues. (B) Probability density of the number of co-expression links identified through the permutation of orthologous miRNAs. The permutation experiment was repeated 100 times. (C) ROC curves used to quantify the significant of these relationships using a PCR-based miRNA expression data (GSE23024).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3285207&req=5

pone-0032201-g001: Evaluation of the conserved co-expression relationships.(A) Pie charts of miRNA expression data from human (top) and mouse (bottom) included in the analysis. Colors represent different tissues. (B) Probability density of the number of co-expression links identified through the permutation of orthologous miRNAs. The permutation experiment was repeated 100 times. (C) ROC curves used to quantify the significant of these relationships using a PCR-based miRNA expression data (GSE23024).
Mentions: We collected 16 human and 8 mouse miRNA expression data sets respectively including 611 and 107 samples (Figure 1A). All expression data sets were generated using Agilent arrays. After normalization and probes mapping, 702 and 490 mature miRNAs were consistently present in human and mouse miRNA expression data sets, respectively. To identify miRNAs that are co-expressed across human and mouse, we identified 285 human-mouse orthologous miRNAs by all-against-all alignment of precursor miRNA (pre-miRNA) sequences with 11 bp flanking regions. Because all expression data sets used in this study are specific for mature miRNAs, we then linked mature miRNAs in human with their corresponding mature miRNAs in mouse according to these 285 orthologous miRNAs. Finally, 341 human-mouse orthologous mature miRNAs were identified. Of these, 253 with both members having expression measurements were used in the following analysis (Table S1).

Bottom Line: Our analysis reveals that many miRNAs in the same sub-network are associated with the same diseases.Our results imply that multiple co-expressed miRNAs can cooperatively regulate a given biological process by targeting common components of that process, and the pathogenesis of disease may be associated with the abnormality of multiple functionally cooperative miRNAs rather than individual miRNAs.In addition, many of these co-expression relationships provide strong evidence for the involvement of new miRNAs in important biological processes, such as apoptosis, differentiation and cell cycle, indicating their potential disease links.

View Article: PubMed Central - PubMed

Affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China.

ABSTRACT
MicroRNAs, a new class of key regulators of gene expression, have been shown to be involved in diverse biological processes and linked to many human diseases. To elucidate miRNA function from a global perspective, we constructed a conserved miRNA co-expression network by integrating multiple human and mouse miRNA expression data. We found that these conserved co-expressed miRNA pairs tend to reside in close genomic proximity, belong to common families, share common transcription factors, and regulate common biological processes by targeting common components of those processes based on miRNA targets and miRNA knockout/transfection expression data, suggesting their strong functional associations. We also identified several co-expressed miRNA sub-networks. Our analysis reveals that many miRNAs in the same sub-network are associated with the same diseases. By mapping known disease miRNAs to the network, we identified three cancer-related miRNA sub-networks. Functional analyses based on targets and miRNA knockout/transfection data consistently show that these sub-networks are significantly involved in cancer-related biological processes, such as apoptosis and cell cycle. Our results imply that multiple co-expressed miRNAs can cooperatively regulate a given biological process by targeting common components of that process, and the pathogenesis of disease may be associated with the abnormality of multiple functionally cooperative miRNAs rather than individual miRNAs. In addition, many of these co-expression relationships provide strong evidence for the involvement of new miRNAs in important biological processes, such as apoptosis, differentiation and cell cycle, indicating their potential disease links.

Show MeSH
Related in: MedlinePlus