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MicroRNA and transcription factor mediated regulatory network analysis reveals critical regulators and regulatory modules in myocardial infarction.

Zhang G, Shi H, Wang L, Zhou M, Wang Z, Liu X, Cheng L, Li W, Li X - PLoS ONE (2015)

Bottom Line: Furthermore, based on the miRNA and TF mediated regulatory network and literature survey, we proposed a pathway model for miR-21-5p, the miR-29 family and SP1 to demonstrate their potential co-regulatory mechanisms in cardiac fibrosis, apoptosis and angiogenesis.The majority of the regulatory relations in the model were confirmed by previous studies, which demonstrated the reliability and validity of this miRNA and TF mediated regulatory network.Our study will aid in deciphering the complex regulatory mechanisms involved in MI and provide putative therapeutic targets for MI.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, PR China.

ABSTRACT
Myocardial infarction (MI) is a severe coronary artery disease and a leading cause of mortality and morbidity worldwide. However, the molecular mechanisms of MI have yet to be fully elucidated. In this study, we compiled MI-related genes, MI-related microRNAs (miRNAs) and known human transcription factors (TFs), and we then identified 1,232 feed-forward loops (FFLs) among these miRNAs, TFs and their co-regulated target genes through integrating target prediction. By merging these FFLs, the first miRNA and TF mediated regulatory network for MI was constructed, from which four regulators (SP1, ESR1, miR-21-5p and miR-155-5p) and three regulatory modules that might play crucial roles in MI were then identified. Furthermore, based on the miRNA and TF mediated regulatory network and literature survey, we proposed a pathway model for miR-21-5p, the miR-29 family and SP1 to demonstrate their potential co-regulatory mechanisms in cardiac fibrosis, apoptosis and angiogenesis. The majority of the regulatory relations in the model were confirmed by previous studies, which demonstrated the reliability and validity of this miRNA and TF mediated regulatory network. Our study will aid in deciphering the complex regulatory mechanisms involved in MI and provide putative therapeutic targets for MI.

No MeSH data available.


Related in: MedlinePlus

Workflow to construct the MI-specific miRNA and TF mediated regulatory network.Step 1: Collecting MIgenes, MImiRNAs and known human TFs from publicly available databases and literature. Step 2: Retrieving regulatory relationships among MIgenes, MImiRNAs and known human TFs using an integrated strategy. Step 3: Identifying three types of FFLs based on the relationships among MIgenes, MImiRNAs and known human TFs. Step 4: Constructing the MI-specific miRNA and TF mediated regulatory network by merging the FFLs obtained in step 3.
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pone.0135339.g001: Workflow to construct the MI-specific miRNA and TF mediated regulatory network.Step 1: Collecting MIgenes, MImiRNAs and known human TFs from publicly available databases and literature. Step 2: Retrieving regulatory relationships among MIgenes, MImiRNAs and known human TFs using an integrated strategy. Step 3: Identifying three types of FFLs based on the relationships among MIgenes, MImiRNAs and known human TFs. Step 4: Constructing the MI-specific miRNA and TF mediated regulatory network by merging the FFLs obtained in step 3.

Mentions: Randomization test was performed to evaluate the significance of the FFLs observed in the set of TFs, MImiRNAs and MIgenes (Fig 1) according to a previous study [13]. In each run of the randomization, the same number of miRNA-gene pairs from all MImiRNA target genes was randomly selected, and the number of FFLs was then calculated. This procedure was implemented 10,000 times, and a p-value was calculated as the proportion of randomly achieved FFLs greater than or equal to the number of true FFLs.


MicroRNA and transcription factor mediated regulatory network analysis reveals critical regulators and regulatory modules in myocardial infarction.

Zhang G, Shi H, Wang L, Zhou M, Wang Z, Liu X, Cheng L, Li W, Li X - PLoS ONE (2015)

Workflow to construct the MI-specific miRNA and TF mediated regulatory network.Step 1: Collecting MIgenes, MImiRNAs and known human TFs from publicly available databases and literature. Step 2: Retrieving regulatory relationships among MIgenes, MImiRNAs and known human TFs using an integrated strategy. Step 3: Identifying three types of FFLs based on the relationships among MIgenes, MImiRNAs and known human TFs. Step 4: Constructing the MI-specific miRNA and TF mediated regulatory network by merging the FFLs obtained in step 3.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4530868&req=5

pone.0135339.g001: Workflow to construct the MI-specific miRNA and TF mediated regulatory network.Step 1: Collecting MIgenes, MImiRNAs and known human TFs from publicly available databases and literature. Step 2: Retrieving regulatory relationships among MIgenes, MImiRNAs and known human TFs using an integrated strategy. Step 3: Identifying three types of FFLs based on the relationships among MIgenes, MImiRNAs and known human TFs. Step 4: Constructing the MI-specific miRNA and TF mediated regulatory network by merging the FFLs obtained in step 3.
Mentions: Randomization test was performed to evaluate the significance of the FFLs observed in the set of TFs, MImiRNAs and MIgenes (Fig 1) according to a previous study [13]. In each run of the randomization, the same number of miRNA-gene pairs from all MImiRNA target genes was randomly selected, and the number of FFLs was then calculated. This procedure was implemented 10,000 times, and a p-value was calculated as the proportion of randomly achieved FFLs greater than or equal to the number of true FFLs.

Bottom Line: Furthermore, based on the miRNA and TF mediated regulatory network and literature survey, we proposed a pathway model for miR-21-5p, the miR-29 family and SP1 to demonstrate their potential co-regulatory mechanisms in cardiac fibrosis, apoptosis and angiogenesis.The majority of the regulatory relations in the model were confirmed by previous studies, which demonstrated the reliability and validity of this miRNA and TF mediated regulatory network.Our study will aid in deciphering the complex regulatory mechanisms involved in MI and provide putative therapeutic targets for MI.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, PR China.

ABSTRACT
Myocardial infarction (MI) is a severe coronary artery disease and a leading cause of mortality and morbidity worldwide. However, the molecular mechanisms of MI have yet to be fully elucidated. In this study, we compiled MI-related genes, MI-related microRNAs (miRNAs) and known human transcription factors (TFs), and we then identified 1,232 feed-forward loops (FFLs) among these miRNAs, TFs and their co-regulated target genes through integrating target prediction. By merging these FFLs, the first miRNA and TF mediated regulatory network for MI was constructed, from which four regulators (SP1, ESR1, miR-21-5p and miR-155-5p) and three regulatory modules that might play crucial roles in MI were then identified. Furthermore, based on the miRNA and TF mediated regulatory network and literature survey, we proposed a pathway model for miR-21-5p, the miR-29 family and SP1 to demonstrate their potential co-regulatory mechanisms in cardiac fibrosis, apoptosis and angiogenesis. The majority of the regulatory relations in the model were confirmed by previous studies, which demonstrated the reliability and validity of this miRNA and TF mediated regulatory network. Our study will aid in deciphering the complex regulatory mechanisms involved in MI and provide putative therapeutic targets for MI.

No MeSH data available.


Related in: MedlinePlus