Deregulated Cardiac Specific MicroRNAs in Postnatal Heart Growth

Abstract

The heart is recognized as an organ that is terminally differentiated by adulthood. However, during the process of human development, the heart is the first organ with function in the embryo and grows rapidly during the postnatal period. MicroRNAs (miRNAs, miRs), as regulators of gene expression, play important roles during the development of multiple systems. However, the role of miRNAs in postnatal heart growth is still unclear. In this study, by using qRT-PCR, we compared the expression of seven cardiac- or muscle-specific miRNAs that may be related to heart development in heart tissue from mice at postnatal days 0, 3, 8, and 14. Four miRNAs—miR-1a-3p, miR-133b-3p, miR-208b-3p, and miR-206-3p—were significantly decreased while miR-208a-3p was upregulated during the postnatal heart growth period. Based on these results, GeneSpring GX was used to predict potential downstream targets by performing a 3-way comparison of predictions from the miRWalk, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to identify potential functional annotations and signaling pathways related to postnatal heart growth. This study describes expression changes of cardiac- and muscle-specific miRNAs during postnatal heart growth and may provide new therapeutic targets for cardiovascular diseases.

miRNAS in cardiovascular diseases: potential biomarkers, therapeutic targets and challenges

“…As discussed above, several miRNAs show promise as markers based on their association with specific or several CVD. For a miRNA to be considered a diagnostic marker of CVD or a potential therapeutic target however, it should be predominantly expressed in cardiac tissue and/or essential for heart development, function, or repair of heart-specific damage, for example, miR-1, miR133a, miR-208a/b, and miR-499 119,120 .…”

Noncoding RNAs in the Cardiovascular System: Exercise Training Effects

“…There is currently evidence that the protective effects of aerobic ET involve changes in pattern expression of specific miRNAs by positively regulating cardiovascular remodeling. In fact, miRNAs play important roles in the regulation of distinct processes in mammals, and although they exhibit limited complementarity with their target RNAs, it is still sufficient for them to regulate various physiological processes, including cell proliferation, differentiation, migration, angiogenesis, apoptosis, tissue development, and remodeling [14,136,137]. However, new studies to understand the pathways and mechanisms in which the ET acts on the miRNAs are required.…”

Emerging roles of microRNA‐208a in cardiology and reverse cardio‐oncology

“…miR‐208a is a component of the network of heart‐enriched miRs, which regulate cardiomyocyte differentiation, myosin content, and muscle performance, as well as cardiac conduction 23,31,33,36 . In rodents, the expression level of miR‐208b is higher in the fetal heart than in the adult heart, whereas cardiac miR‐208a expression is low during heart development but increases in adulthood 21,23,32 . miR‐208a plays important roles in heart development by regulating Cut‐like homeobox 1 (CUX1), a transcriptional repressor of genes specifying terminal differentiation (Figure 1).…”

“…As an important modulator of cardiovascular physiology and diseases, 21‐24 miR‐208a , a member of the miR‐208 family (Box 1), also plays important roles in modulating cancer biology 25‐30 . With respect to cardiovascular development and normal growth, miR‐208a functions as an important regulator of multiple gene networks associated with cardiac conduction and contraction 23,31‐33 .…”