Systematic identification and analysis of dysregulated mi RNA and transcription factor feed‐forward loops in hypertrophic cardiomyopathy

Abstract Hypertrophic cardiomyopathy ( HCM ) is the most common genetic cardiovascular disease. Although some genes and mi RNA s related with HCM have been studied, the molecular regulatory mechanisms between mi RNA s and transcription factors ( TF s) in HCM have not been systematically elucidated. In this study, we proposed a novel method for identifying dysregulated mi RNA ‐ TF feed‐forward loops ( FFL s) by integrating sample matched mi RNA and gene expression profiles and experimentally verified interactions of TF ‐target gene and mi RNA ‐target gene. We identified 316 dysregulated mi RNA ‐ TF FFL s 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 mi RNA s and TF s in HCM , and the FFL composed of hsa‐miR‐17‐5p, FASN and STAT 3 was inferred to play critical roles in HCM . Additionally, we identified two panels of biomarkers defined by three TF s ( CEBPB , HIF 1A, and STAT 3) and four mi RNA s (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 mi RNA ‐ TF FFL s for further experimental study, and provides candidate biomarkers for HCM diagnosis and treatment.