Long Noncoding RNA LncBAR Enhances BRG1 Protein to Promote Cardiomyocyte Cell Cycle Progression and Cardiac Repair

The mammalian heart retains regenerative capacity during the early postnatal period, but this ability declines as it matures. Enhancing cardiomyocyte proliferation represents a key therapeutic approach to promote heart regeneration and repair, yet the molecular mechanisms remain elusive. Here, we identified LncBAR (BAF complex-associated lncRNA) as a critical regulator of cardiac regeneration. LncBAR expression declines during heart development but is upregulated following cardiac injury. Loss of LncBAR impairs cardiomyocyte growth, suppresses cell cycle gene expression, and diminishes heart regeneration, as evidenced by reduced cytokinesis and cardiac function. Conversely, cardiac specific overexpression of LncBAR restores cardiomyocyte proliferation and enhances cardiac regeneration, especially in adult myocardial infarction model. Mechanistically, LncBAR interacts with Brg1, stabilizing BRG1 protein level and activating cell cycle progression to drive cardiomyocytes proliferation. Collectively, our study identified LncBAR as a crucial regulator for heart regeneration, highlighting the LncBAR-BRG1 axis as a promising therapeutic strategy for cardiac repair. Overall design: To investigate the function of LncBAR in regulating the proliferation of mouse cardiomyocytes, we isolated primary neonatal mouse cardiomyocytes to perform loss-of-function or gain-of-function experiments To explore the effect of LncBAR on cardiac regeneration, we constructed an AR model of LncBAR knockout mice and LncBAR transgenic mice To explore the effect of LncBAR on adult cardiac regeneration, we constructed an MI model of LncBAR transgenic mice To explore the mechanism of LncBAR regulates cardiomyocyte proliferation, we performed RNA seq of LncBAR knockdown in cardiomyocytes