Limits...
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

Three modules in the MI-specific miRNA and TF mediated network.The nodes in the orange box denote hub nodes, and the nodes in the purple box denote having a top 5% betweenness centrality in the network.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4530868&req=5

pone.0135339.g003: Three modules in the MI-specific miRNA and TF mediated network.The nodes in the orange box denote hub nodes, and the nodes in the purple box denote having a top 5% betweenness centrality in the network.

Mentions: As shown in Fig 3A, the first module contained 15 nodes (3 MIgenes, 5 MImiRNAs and 7 MITFs). Among the 15 nodes, 9 (60.00%) were hub nodes, and 3 (20.00%) were ranked in the top 5% of 433 nodes in the network for betweenness centrality. Three (miR-29a-3p, miR-29b-3p and miR-29c-3p) of the 5 MImiRNAs belonged to the miR-29 family, members of which are known to target a cadre of protein-coding mRNAs involved in fibrosis and play crucial roles in cardiac fibrosis [46]. Further examination was performed to determine whether the genes in this module have more similar function than randomly selected MIgenes. GO semantic similarity scores based on the three sub-ontologies (biological process, molecular function and cellular component) were calculated among genes using the R GOSemSim package [40] (see Materials and Methods). The results indicated that the gene pairs in this module tended to have significantly higher semantic similarity scores than those of randomly selected MIgene pairs (S2 Fig). In addition, we investigated the important role of this module in MI-specific miRNA and TF mediated network. The module was removed and the connectivity of the network was tested. As a result, closeness centrality was significantly lower than that of original network (p-value = 8.32×10−7, t-test), which demonstrated the importance of the community in communicating information with other molecules in the network.


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)

Three modules in the MI-specific miRNA and TF mediated network.The nodes in the orange box denote hub nodes, and the nodes in the purple box denote having a top 5% betweenness centrality in the network.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0135339.g003: Three modules in the MI-specific miRNA and TF mediated network.The nodes in the orange box denote hub nodes, and the nodes in the purple box denote having a top 5% betweenness centrality in the network.
Mentions: As shown in Fig 3A, the first module contained 15 nodes (3 MIgenes, 5 MImiRNAs and 7 MITFs). Among the 15 nodes, 9 (60.00%) were hub nodes, and 3 (20.00%) were ranked in the top 5% of 433 nodes in the network for betweenness centrality. Three (miR-29a-3p, miR-29b-3p and miR-29c-3p) of the 5 MImiRNAs belonged to the miR-29 family, members of which are known to target a cadre of protein-coding mRNAs involved in fibrosis and play crucial roles in cardiac fibrosis [46]. Further examination was performed to determine whether the genes in this module have more similar function than randomly selected MIgenes. GO semantic similarity scores based on the three sub-ontologies (biological process, molecular function and cellular component) were calculated among genes using the R GOSemSim package [40] (see Materials and Methods). The results indicated that the gene pairs in this module tended to have significantly higher semantic similarity scores than those of randomly selected MIgene pairs (S2 Fig). In addition, we investigated the important role of this module in MI-specific miRNA and TF mediated network. The module was removed and the connectivity of the network was tested. As a result, closeness centrality was significantly lower than that of original network (p-value = 8.32×10−7, t-test), which demonstrated the importance of the community in communicating information with other molecules in the network.

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