Non-coding RNAs in cardiac regeneration: Mechanism of action and therapeutic potential

In the past two decades, thousands of non-coding RNAs (ncRNAs) have been discovered, annotated, and char-acterized in nearly every tissue under both physiological and pathological conditions. Here, we will focus on the role of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circR-NAs) in ischemic heart disease (IHD), which remains the leading cause of morbidity and mortality in human-s-resulting in 8.9 million deaths annually. Cardiomyocyte (CM) proliferation, differentiation, and survival in addition to neovascularization of injured tissues and the prevention of fibrosis are commonly regarded as crit-ically important for the recovery of the heart following myocardial infarction (MI). An abundance of evidence has been accumulated to show ncRNAs participate in cardiac recovery after MI. Because miRNAs are important regulators of cardiac regeneration, the therapeutic potential of at least five of these molecules has been assessed in large animal models of human IHD. In particular, miRNA-based interventions based on miR-132 and miR-92a inhibition in related diseases have displayed favorable outcomes that have provided the impetus for miRNA-based clinical trials for IHD. At the same time, the functional roles of lncRNAs and circRNAs in cardiac regen-eration are also being explored. In the present review, we will summarize the latest ncRNA studies aimed at reversing damage to the ischemic heart and discuss the therapeutic potential of targeting miRNAs, lncRNAs, and circRNAs to stimulate cardiac regeneration.

Automated summary

In the past two decades, ncRNAs, especially miRNAs, lncRNAs, and circRNAs, have been found to play important roles in ischemic heart disease, participating in the process of cardiac recovery. Studies have shown that at least five miRNAs have therapeutic potential in large animal models, with favorable outcomes. Furthermore, the functional roles of lncRNAs and circRNAs are also being explored in cardiac regeneration.