Systematic identification and analysis of dysregulated miRNA and transcription factor feed-forward loops in hypertrophic cardiomyopathy.

Abstract

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.

• Authors: Hongbo Shi, Jiayao Li, Qiong Song, Liang Cheng, Haoran Sun, Wenjing Fan, Jianfei Li, Zhenzhen Wang, Guangde Zhang
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 23 Issue 1 Pg. 306-316 (01 2019) ISSN: 1582-4934 [Electronic] England
• PMID: 30338905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Biomarkers
• MicroRNAs
• STAT3 Transcription Factor
• STAT3 protein, human
• Transcription Factors

Topics

• Biomarkers
• Cardiomyopathy, Hypertrophic (genetics)
• Feedback, Physiological
• Gene Expression Profiling
• Gene Regulatory Networks
• Humans
• MicroRNAs (genetics)
• Reproducibility of Results
• STAT3 Transcription Factor (genetics)
• Transcription Factors (genetics)