title: Studying Dynamic Features in Myocardial Infarction Progression by Integrating miRNA-Transcription Factor Co-Regulatory Networks and Time-Series RNA Expression Data from Peripheral Blood Mononuclear Cells.
abstract: Myocardial infarction (MI) is a serious heart disease and a leading cause of mortality and morbidity worldwide. Although some molecules (genes, miRNAs and transcription factors (TFs)) associated with MI have been studied in a specific pathological context, their dynamic characteristics in gene expressions, biological functions and regulatory interactions in MI progression have not been fully elucidated to date. In the current study, we analyzed time-series RNA expression data from peripheral blood mononuclear cells. We observed that significantly differentially expressed genes were sharply up- or down-regulated in the acute phase of MI, and then changed slowly until the chronic phase. Biological functions involved at each stage of MI were identified. Additionally, dynamic miRNA-TF co-regulatory networks were constructed based on the significantly differentially expressed genes and miRNA-TF co-regulatory motifs, and the dynamic interplay of miRNAs, TFs and target genes were investigated. Finally, a new panel of candidate diagnostic biomarkers (STAT3 and ICAM1) was identified to have discriminatory capability for patients with or without MI, especially the patients with or without recurrent events. The results of the present study not only shed new light on the understanding underlying regulatory mechanisms involved in MI progression, but also contribute to the discovery of true diagnostic biomarkers for MI.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, 150081, PR China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, PR China.
authors.forename: Guangde
authors.initials: G
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, 150081, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, 150081, PR China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, PR China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Liu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, 150081, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, PR China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Li
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D019295:Computational Biology; D018450:Disease Progression; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D009203:Myocardial Infarction / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D014157:Transcription Factors