Systematic identification and analysis of dysregulated miRNA and transcription factor feed-forward loops in hypertrophic cardiomyopathy.
feed-forward loop
miRNA
transcription factor
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
27
04
2018
accepted:
30
08
2018
pubmed:
20
10
2018
medline:
12
6
2020
entrez:
20
10
2018
Statut:
ppublish
Résumé
Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease. Although some genes and miRNAs related with HCM have been studied, the molecular regulatory mechanisms between miRNAs and transcription factors (TFs) in HCM have not been systematically elucidated. In this study, we proposed a novel method for identifying dysregulated miRNA-TF feed-forward loops (FFLs) by integrating sample matched miRNA and gene expression profiles and experimentally verified interactions of TF-target gene and miRNA-target gene. We identified 316 dysregulated miRNA-TF FFLs in HCM, which were confirmed to be closely related with HCM from various perspectives. Subpathway enrichment analysis demonstrated that the method was outperformed by the existing method. Furthermore, we systematically analysed the global architecture and feature of gene regulation by miRNAs and TFs in HCM, and the FFL composed of hsa-miR-17-5p, FASN and STAT3 was inferred to play critical roles in HCM. Additionally, we identified two panels of biomarkers defined by three TFs (CEBPB, HIF1A, and STAT3) and four miRNAs (hsa-miR-155-5p, hsa-miR-17-5p, hsa-miR-20a-5p, and hsa-miR-181a-5p) in a discovery cohort of 126 samples, which could differentiate HCM patients from healthy controls with better performance. Our work provides HCM-related dysregulated miRNA-TF FFLs for further experimental study, and provides candidate biomarkers for HCM diagnosis and treatment.
Identifiants
pubmed: 30338905
doi: 10.1111/jcmm.13928
pmc: PMC6307764
doi:
Substances chimiques
Biomarkers
0
MicroRNAs
0
STAT3 Transcription Factor
0
STAT3 protein, human
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
306-316Informations de copyright
© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
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