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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

Model of co-regulation of miR-21-5p, the miR-29 family and SP1 involving a biological pathway and the regulatory network.After MI, the expression of TNF-α, IL-6 and TGF-β increased and activated several biological pathways, including JAK and PI3K/AKT pathways. These signal transductions activated several TFs, such as NFκB, STAT3 and SP1, to promote the transcription of miRNAs (e.g. mir-21) and genes (e.g. TIMP3, VEGFA, FASLG and COL4A1). miR-21-5p, the miR-29 family and SP1 co-regulated the process of cardiac fibrosis, apoptosis and angiogenesis through several cascades.
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pone.0135339.g004: Model of co-regulation of miR-21-5p, the miR-29 family and SP1 involving a biological pathway and the regulatory network.After MI, the expression of TNF-α, IL-6 and TGF-β increased and activated several biological pathways, including JAK and PI3K/AKT pathways. These signal transductions activated several TFs, such as NFκB, STAT3 and SP1, to promote the transcription of miRNAs (e.g. mir-21) and genes (e.g. TIMP3, VEGFA, FASLG and COL4A1). miR-21-5p, the miR-29 family and SP1 co-regulated the process of cardiac fibrosis, apoptosis and angiogenesis through several cascades.

Mentions: To explore the potential co-regulatory mechanisms between miRNAs and TFs in MI, a pathway model demonstrating the co-regulation of miR-21-5p, the miR-29 family (miR-29a-3p, miR-29b-3p and miR-29c-3p) and SP1 in cardiac fibrosis, apoptosis and angiogenesis was proposed (Fig 4). This pathway model was constructed based on the constructed MI-specific miRNA and TF mediated regulatory network and a comprehensive literature review (S3 Fig and S6 Table).


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)

Model of co-regulation of miR-21-5p, the miR-29 family and SP1 involving a biological pathway and the regulatory network.After MI, the expression of TNF-α, IL-6 and TGF-β increased and activated several biological pathways, including JAK and PI3K/AKT pathways. These signal transductions activated several TFs, such as NFκB, STAT3 and SP1, to promote the transcription of miRNAs (e.g. mir-21) and genes (e.g. TIMP3, VEGFA, FASLG and COL4A1). miR-21-5p, the miR-29 family and SP1 co-regulated the process of cardiac fibrosis, apoptosis and angiogenesis through several cascades.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0135339.g004: Model of co-regulation of miR-21-5p, the miR-29 family and SP1 involving a biological pathway and the regulatory network.After MI, the expression of TNF-α, IL-6 and TGF-β increased and activated several biological pathways, including JAK and PI3K/AKT pathways. These signal transductions activated several TFs, such as NFκB, STAT3 and SP1, to promote the transcription of miRNAs (e.g. mir-21) and genes (e.g. TIMP3, VEGFA, FASLG and COL4A1). miR-21-5p, the miR-29 family and SP1 co-regulated the process of cardiac fibrosis, apoptosis and angiogenesis through several cascades.
Mentions: To explore the potential co-regulatory mechanisms between miRNAs and TFs in MI, a pathway model demonstrating the co-regulation of miR-21-5p, the miR-29 family (miR-29a-3p, miR-29b-3p and miR-29c-3p) and SP1 in cardiac fibrosis, apoptosis and angiogenesis was proposed (Fig 4). This pathway model was constructed based on the constructed MI-specific miRNA and TF mediated regulatory network and a comprehensive literature review (S3 Fig and S6 Table).

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