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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

MI-specific miRNA and TF mediated regulatory network and its structure and functional features.(A). The MI-specific miRNA and TF mediated regulatory network was composed of MIgenes (circles), MImiRNAs (triangles) and TFs (diamonds). This network consists of 438 nodes and 1,780 links. (B). Degree distribution of all the nodes in the network, and degree distribution of genes, miRNAs and TFs in the network. (C). Significantly-enriched KEGG pathways for MIgenes in the network (cancer pathways removed). p-value was adjusted using the Benjamini-Hochberg multiple testing correction and a p-value of <0.05 was used as a threshold to select significant KEGG pathways. ‘*’ indicated the pathways belonged to cardiovascular disease pathways in KEGG.
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pone.0135339.g002: MI-specific miRNA and TF mediated regulatory network and its structure and functional features.(A). The MI-specific miRNA and TF mediated regulatory network was composed of MIgenes (circles), MImiRNAs (triangles) and TFs (diamonds). This network consists of 438 nodes and 1,780 links. (B). Degree distribution of all the nodes in the network, and degree distribution of genes, miRNAs and TFs in the network. (C). Significantly-enriched KEGG pathways for MIgenes in the network (cancer pathways removed). p-value was adjusted using the Benjamini-Hochberg multiple testing correction and a p-value of <0.05 was used as a threshold to select significant KEGG pathways. ‘*’ indicated the pathways belonged to cardiovascular disease pathways in KEGG.

Mentions: We constructed a miRNA and TF mediated regulatory network specific for MI by merging the three types of FFLs identified in the above subsection (Fig 2A). The network included 438 unique nodes (60 MImiRNAs, 256 MIgenes and 141 TFs). Among 256 MIgenes and 141 TFs, 19 common genes (APEX1, BRCA1, CREB1, CREM, ESR1, ESR2, FOS, FOXO3, HIF1A, MEF2A, NFκB1, NFYC, NR3C1, PPARA, PPARG, SP1, SREBF2, STAT3 and TP53) were observed. To more clearly analyse the features of the regulators separated from the other genes, we considered these genes only in the TF set and referred to them as MITFs. Thus, there were 438 unique nodes (60 MImiRNAs, 237 MIgenes and 141 MITFs) and 1,780 interactions in the network (S2 Table). Among the 1,780 interactions, 529 belonged to miRNA-gene pairs, 382 belonged to miRNA-TF pairs, 680 belonged to TF-gene pairs, 83 belonged to TF-miRNA pairs and 106 belonged to TF-TF pairs.


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)

MI-specific miRNA and TF mediated regulatory network and its structure and functional features.(A). The MI-specific miRNA and TF mediated regulatory network was composed of MIgenes (circles), MImiRNAs (triangles) and TFs (diamonds). This network consists of 438 nodes and 1,780 links. (B). Degree distribution of all the nodes in the network, and degree distribution of genes, miRNAs and TFs in the network. (C). Significantly-enriched KEGG pathways for MIgenes in the network (cancer pathways removed). p-value was adjusted using the Benjamini-Hochberg multiple testing correction and a p-value of <0.05 was used as a threshold to select significant KEGG pathways. ‘*’ indicated the pathways belonged to cardiovascular disease pathways in KEGG.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0135339.g002: MI-specific miRNA and TF mediated regulatory network and its structure and functional features.(A). The MI-specific miRNA and TF mediated regulatory network was composed of MIgenes (circles), MImiRNAs (triangles) and TFs (diamonds). This network consists of 438 nodes and 1,780 links. (B). Degree distribution of all the nodes in the network, and degree distribution of genes, miRNAs and TFs in the network. (C). Significantly-enriched KEGG pathways for MIgenes in the network (cancer pathways removed). p-value was adjusted using the Benjamini-Hochberg multiple testing correction and a p-value of <0.05 was used as a threshold to select significant KEGG pathways. ‘*’ indicated the pathways belonged to cardiovascular disease pathways in KEGG.
Mentions: We constructed a miRNA and TF mediated regulatory network specific for MI by merging the three types of FFLs identified in the above subsection (Fig 2A). The network included 438 unique nodes (60 MImiRNAs, 256 MIgenes and 141 TFs). Among 256 MIgenes and 141 TFs, 19 common genes (APEX1, BRCA1, CREB1, CREM, ESR1, ESR2, FOS, FOXO3, HIF1A, MEF2A, NFκB1, NFYC, NR3C1, PPARA, PPARG, SP1, SREBF2, STAT3 and TP53) were observed. To more clearly analyse the features of the regulators separated from the other genes, we considered these genes only in the TF set and referred to them as MITFs. Thus, there were 438 unique nodes (60 MImiRNAs, 237 MIgenes and 141 MITFs) and 1,780 interactions in the network (S2 Table). Among the 1,780 interactions, 529 belonged to miRNA-gene pairs, 382 belonged to miRNA-TF pairs, 680 belonged to TF-gene pairs, 83 belonged to TF-miRNA pairs and 106 belonged to TF-TF pairs.

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