MicroRNA‐101 Protects Against Cardiac Remodeling Following Myocardial Infarction via Downregulation of Runt‐Related Transcription Factor 1

BACKGROUND: Myocardial infarction (MI) generally leads to heart failure and sudden death. The hearts of people with MI undergo remodeling with the features of expanded myocardial infarct size and dilated left ventricle. Many microRNAs (miRs) have been revealed to be involved in the remodeling process; however, the participation of miR‐101 remains unknown. Therefore, this study aims to find out the regulatory mechanism of miR‐101 in MI‐induced cardiac remodeling. METHODS AND RESULTS: Microarray data analysis was conducted to screen differentially expressed genes in MI. The rat model of MI was established by left coronary artery ligation. In addition, the relationship between miR‐101 and runt‐related transcription factor 1 (RUNX1) was identified using dual luciferase reporter assay. After that, the rats injected with lentiviral vector expressing miR‐101 mimic, inhibitor, or small interfering RNA against RUNX1 were used to examine the effects of miR‐101 and RUNX1 on transforming growth factor β signaling pathway, cardiac function, infarct size, myocardial fibrosis, and cardiomyocyte apoptosis. RUNX1 was highly expressed, while miR‐101 was poorly expressed in MI. miR‐101 was identified to target RUNX1. Following that, it was found that overexpression of miR‐101 or silencing of RUNX1 improved the cardiac function and elevated left ventricular end‐diastolic and end‐systolic diameters. Also, miR‐101 elevation or RUNX1 depletion decreased infarct size, myocardial fibrosis, and cardiomyocyte apoptosis. Moreover, miR‐101 could negatively regulate RUNX1 to inactivate the transforming growth factor β1/Smad family member 2 signaling pathway. CONCLUSIONS: Taken together, miR‐101 plays a protective role against cardiac remodeling following MI via inactivation of the RUNX1‐dependent transforming growth factor β1/Smad family member 2 signaling pathway, proposing miR‐101 and RUNX1 as potential therapeutic targets for MI.