Overexpression of the long non-coding RNA ECRAR stimulated myocardial regeneration and induced recovery of cardiac function after myocardial infarction in rat models.
Does ECRAR overexpression promote myocardial regeneration and recovery of cardiac function after myocardial infarction in preclinical models?
The discovery of the lncRNA ECRAR and its role in driving cardiomyocyte proliferation via ERK1/2 signaling highlights a novel therapeutic target for cardiac regeneration in heart failure.
Reactivating post-natal myocardial regeneration potential may be a feasible strategy to regenerate the injured adult heart. Long non-coding RNAs (lncRNAs) have been implicated in regulating cellular differentiation, but whether they can elicit a regenerative response in the post-natal heart remains unknown. In this study, by characterizing the lncRNA transcriptome in human hearts during the fetal-to-adult transition, we found that 3,092 lncRNAs were differentially expressed, and we further identified a novel upregulated fetal lncRNA that we called endogenous cardiac regeneration-associated regulator (ECRAR), which promoted DNA synthesis, mitosis, and cytokinesis in post-natal day 7 and adult rat cardiomyocytes (CMs). Overexpression of ECRAR markedly stimulated myocardial regeneration and induced recovery of cardiac function after myocardial infarction (MI). Knockdown of ECRAR inhibited post-natal day 1 CM proliferation and prevented post-MI recovery. ECRAR was transcriptionally upregulated by E2F transcription factor 1 (E2F1). In addition, ECRAR directly bound to and promoted the phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), resulting in downstream targets of cyclin D1 and cyclin E1 activation, which, in turn, activated E2F1. The E2F1-ECRAR-ERK1/2 signaling formed a positive feedback loop to drive cell cycle progression, and, therefore, it promoted CM proliferation. These findings indicated that our newly discovered ECRAR may be a valuable therapeutic target for heart failure.
Chen et al. (Thu,) conducted a other in Myocardial infarction. ECRAR overexpression was evaluated on Myocardial regeneration and recovery of cardiac function. Overexpression of the long non-coding RNA ECRAR stimulated myocardial regeneration and induced recovery of cardiac function after myocardial infarction in rat models.