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MicroRNA expression analysis: clinical advantage of propranolol reveals key microRNAs in myocardial infarction.

Zhu W, Yang L, Shan H, Zhang Y, Zhou R, Su Z, Du Z - PLoS ONE (2011)

Bottom Line: Working on a hypothesis that modulation of only some key members in the miRNA superfamily could benefit ischemic heart, we proposed a microarray based network biology approach to identify them with the recognized clinical effect of propranolol as a prompt.Microarray data analysis indicated that long-term propranolol administration caused 18 of the 31 dysregulated miRNAs in MI undergoing reversed expression, implying that intentional modulation of miRNA expression might show favorable effects for ischemic heart.Further finding revealed that miR-1 focused on regulation of myocyte growth, yet miR-29b and miR-98 stressed on fibrosis and inflammation, respectively.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

ABSTRACT

Background: As playing important roles in gene regulation, microRNAs (miRNAs) are believed as indispensable involvers in the pathogenesis of myocardial infarction (MI) that causes significant morbidity and mortality. Working on a hypothesis that modulation of only some key members in the miRNA superfamily could benefit ischemic heart, we proposed a microarray based network biology approach to identify them with the recognized clinical effect of propranolol as a prompt.

Methods: A long-term MI model of rat was established in this study. The microarray technology was applied to determine the global miRNA expression change intervened by propranolol. Multiple network analyses were sequentially applied to evaluate the regulatory capacity, efficiency and emphasis of the miRNAs which dysexpression in MI were significantly reversed by propranolol.

Results: Microarray data analysis indicated that long-term propranolol administration caused 18 of the 31 dysregulated miRNAs in MI undergoing reversed expression, implying that intentional modulation of miRNA expression might show favorable effects for ischemic heart. Our network analysis identified that, among these miRNAs, the prime players in MI were miR-1, miR-29b and miR-98. Further finding revealed that miR-1 focused on regulation of myocyte growth, yet miR-29b and miR-98 stressed on fibrosis and inflammation, respectively.

Conclusion: Our study illustrates how a combination of microarray technology and functional protein network analysis can be used to identify disease-related key miRNAs.

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Related in: MedlinePlus

Results of static and dynamic network analyses.A. Static scores of the 29 dysregulated miRNAs in myocardial infarction.                            B. Correlation between static score and dynamic score. C. Correlation                            between average target gene abundance (log2) and dynamic score.                            non-PRmiR, dysregulated miRNA in myocardial infarction which expression                            could not be reversed by propranolol; PRmiR, propranolol-reversed                            miRNAs.
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pone-0014736-g002: Results of static and dynamic network analyses.A. Static scores of the 29 dysregulated miRNAs in myocardial infarction. B. Correlation between static score and dynamic score. C. Correlation between average target gene abundance (log2) and dynamic score. non-PRmiR, dysregulated miRNA in myocardial infarction which expression could not be reversed by propranolol; PRmiR, propranolol-reversed miRNAs.

Mentions: To perform static topological analysis, a cardiac-specific PPI network was established in advance by importing heart expressed genes of MI Wistar rats (accession number: GDS808) [12] into STRING [13]. The final network was comprised of 2846 nodes and 22163 interactions, when determined at the relatively high confidence level of 0.7. After the validated and predicted target genes [14], [15] associated with the MI-dysregulated miRNAs listed in Table S1 were imported into the network, the Cytoscape [16] plug-in NetworkAnalyzer [17] was applied for calculating static score (See MATERIALS AND METHODS). There were 10 PRmiRs and 7 non-PRmiRs assigned with static scores of more than 0.6 suggesting enhanced regulation by them (Figure 2A). To further confirm the result of static analysis upon the cardiac-specific network, a larger PPI network was also established by importing the target genes of all the chip detected miRNAs into STRING. As a result, we obtained the miRNA-targeted PPI network, which was comprised of 4940 nodes and 88776 interactions at the same confidence level of 0.7. Similarly, we calculated the static scores of the MI-dysregulated miRNAs (Figure 2A). Notably, only 4 PRmiRs showed strengthened regulation in both of the PPI networks. They were miR-1, miR-21, miR-195 and miR-200c. And 2 non-PRmiRs let-7f and miR-208 did so.


MicroRNA expression analysis: clinical advantage of propranolol reveals key microRNAs in myocardial infarction.

Zhu W, Yang L, Shan H, Zhang Y, Zhou R, Su Z, Du Z - PLoS ONE (2011)

Results of static and dynamic network analyses.A. Static scores of the 29 dysregulated miRNAs in myocardial infarction.                            B. Correlation between static score and dynamic score. C. Correlation                            between average target gene abundance (log2) and dynamic score.                            non-PRmiR, dysregulated miRNA in myocardial infarction which expression                            could not be reversed by propranolol; PRmiR, propranolol-reversed                            miRNAs.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3046111&req=5

pone-0014736-g002: Results of static and dynamic network analyses.A. Static scores of the 29 dysregulated miRNAs in myocardial infarction. B. Correlation between static score and dynamic score. C. Correlation between average target gene abundance (log2) and dynamic score. non-PRmiR, dysregulated miRNA in myocardial infarction which expression could not be reversed by propranolol; PRmiR, propranolol-reversed miRNAs.
Mentions: To perform static topological analysis, a cardiac-specific PPI network was established in advance by importing heart expressed genes of MI Wistar rats (accession number: GDS808) [12] into STRING [13]. The final network was comprised of 2846 nodes and 22163 interactions, when determined at the relatively high confidence level of 0.7. After the validated and predicted target genes [14], [15] associated with the MI-dysregulated miRNAs listed in Table S1 were imported into the network, the Cytoscape [16] plug-in NetworkAnalyzer [17] was applied for calculating static score (See MATERIALS AND METHODS). There were 10 PRmiRs and 7 non-PRmiRs assigned with static scores of more than 0.6 suggesting enhanced regulation by them (Figure 2A). To further confirm the result of static analysis upon the cardiac-specific network, a larger PPI network was also established by importing the target genes of all the chip detected miRNAs into STRING. As a result, we obtained the miRNA-targeted PPI network, which was comprised of 4940 nodes and 88776 interactions at the same confidence level of 0.7. Similarly, we calculated the static scores of the MI-dysregulated miRNAs (Figure 2A). Notably, only 4 PRmiRs showed strengthened regulation in both of the PPI networks. They were miR-1, miR-21, miR-195 and miR-200c. And 2 non-PRmiRs let-7f and miR-208 did so.

Bottom Line: Working on a hypothesis that modulation of only some key members in the miRNA superfamily could benefit ischemic heart, we proposed a microarray based network biology approach to identify them with the recognized clinical effect of propranolol as a prompt.Microarray data analysis indicated that long-term propranolol administration caused 18 of the 31 dysregulated miRNAs in MI undergoing reversed expression, implying that intentional modulation of miRNA expression might show favorable effects for ischemic heart.Further finding revealed that miR-1 focused on regulation of myocyte growth, yet miR-29b and miR-98 stressed on fibrosis and inflammation, respectively.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

ABSTRACT

Background: As playing important roles in gene regulation, microRNAs (miRNAs) are believed as indispensable involvers in the pathogenesis of myocardial infarction (MI) that causes significant morbidity and mortality. Working on a hypothesis that modulation of only some key members in the miRNA superfamily could benefit ischemic heart, we proposed a microarray based network biology approach to identify them with the recognized clinical effect of propranolol as a prompt.

Methods: A long-term MI model of rat was established in this study. The microarray technology was applied to determine the global miRNA expression change intervened by propranolol. Multiple network analyses were sequentially applied to evaluate the regulatory capacity, efficiency and emphasis of the miRNAs which dysexpression in MI were significantly reversed by propranolol.

Results: Microarray data analysis indicated that long-term propranolol administration caused 18 of the 31 dysregulated miRNAs in MI undergoing reversed expression, implying that intentional modulation of miRNA expression might show favorable effects for ischemic heart. Our network analysis identified that, among these miRNAs, the prime players in MI were miR-1, miR-29b and miR-98. Further finding revealed that miR-1 focused on regulation of myocyte growth, yet miR-29b and miR-98 stressed on fibrosis and inflammation, respectively.

Conclusion: Our study illustrates how a combination of microarray technology and functional protein network analysis can be used to identify disease-related key miRNAs.

Show MeSH
Related in: MedlinePlus