MiRNA in cardiac development and regeneration

Ke Wei,Zhaohui Ouyang

doi:10.1186/s13619-021-00077-5

Abstract

Ischemic heart disease is one of the main causes of morbidity and mortality in the world. In adult mammalian hearts, most cardiomyocytes are terminally differentiated and have extremely limited capacity of proliferation, making it impossible to regenerate the heart after injuries such as myocardial infarction. MicroRNAs (miRNAs), a class of non-coding single-stranded RNA, which are involved in mRNA silencing and the regulation of post-transcriptional gene expression, have been shown to play a crucial role in cardiac development and cardiomyocyte proliferation. Muscle specific miRNAs such as miR-1 are key regulators of cardiomyocyte maturation and growth, while miR-199-3p and other miRNAs display potent activity to induce proliferation of cardiomyocytes. Given their small size and relative pleiotropic effects, miRNAs have gained significant attraction as promising therapeutic targets or tools in cardiac regeneration. Increasing number of studies demonstrated that overexpression or inhibition of specific miRNAs could induce cardiomyocyte proliferation and cardiac regeneration. Some common targets of pro-proliferation miRNAs, such as the Hippo-Yap signaling pathway, were identified in multiple species, highlighting the power of miRNAs as probes to dissect core regulators of biological processes. A number of miRNAs have been shown to improve heart function after myocardial infarction in mice, and one trial in swine also demonstrated promising outcomes. However, technical difficulties, especially in delivery methods, and adverse effects, such as uncontrolled proliferation, remain. In this review, we summarize the recent progress in miRNA research in cardiac development and regeneration, examine the mechanisms of miRNA regulating cardiomyocyte proliferation, and discuss its potential as a new strategy for cardiac regeneration therapy.

Highlights

As one of the most important organs, the heart is the engine of the blood flow in our body, pushes blood through every organ and tissue to supply oxygen and various nutrients
In the last few decades, microRNA is emerging to be an important regulator of virtually all biological processes in mammals, and its involvement in cardiac development, diseases and regeneration has been gradually discovered, and its potential to be utilized in therapeutics has gained attraction due to its small size and pleiotropic effects
One key characteristic of cardiomyocytes in mammals is that most of them cease to proliferate after birth, and will not regeneration after cardiac injury in adults, leaving cardiac regeneration the greatest challenge in treating cardiac diseases. microRNAs have been demonstrated to be important in this process, as some cardiac specific miRNAs required for mature phenotypes of the cardiomyocytes inhibit proliferation, while other miRNAs promote cardiomyocyte proliferation (Braga et al 2020)

Summary

Introduction

As one of the most important organs, the heart is the engine of the blood flow in our body, pushes blood through every organ and tissue to supply oxygen and various nutrients. Growing amount of evidence has demonstrated that microRNAs (miRNAs), small non-coding RNA which regulate post-translational expression of their target genes, play key roles in cardiac development, cardiomyocyte proliferation and heart regeneration (Braga et al 2020).

Results

Conclusion