MicroRNAs (or miRNAs) represent an abundant class of small, conserved, non-coding RNAs (approximately 22 nucleotides in length) that direct post-transcriptional regulation of gene expression. In complex organisms, miRNAs regulate a wide range of biological processes, including development, differentiation, proliferation, cell metabolism and apoptosis (programmed cell death).
Dysregulation of individual or subset of miRNAs is linked with the pathogenesis of human diseases, such as cancer, cardiovascular disorders, viral infections and metabolic diseases. The first insight into their function was a result of phenotypic studies of mutations that disrupt basic components of the miRNA pathway.
As mentioned before, the primary role of miRNAs is gene regulation; today it is know that they regulate the expression of more than 10 000 genes in a single cell. Such cellular effects of miRNAs can be seen in a myriad of different cells – i.e. in cancer cells, cardiovascular cells or skin cells.
miRNAs in cardiovascular cells
miR-1 is involved in cardiac muscle differentiation and maintenance of muscle gene expression in both mammals and flies. miR-1 promotes the differentiation of precardiac mesoderm into cardiomyocytes and modulates the effects of critical cardiac regulatory proteins in order to control the fine balance between differentiation and proliferation during cardiogenesis.
Several miRNAs (such as miR-126, miR-143 and miR-145) are involved in regulation of complex remodeling processed of lumenized tubes, as well as recruitment of vascular smooth muscle cells to the endothelial plexus during vascular development. Furthermore, miR-126 is implicated in the maintenance of vascular integrity by targeting molecules involved in vascular remodeling and inflammation.
A direct link between miR21 and smooth muscle cell proliferation in response to platelet-derived growth factor-BB (as well as other stimuli) has been observed. That particular miRNA is upregulated in proliferative vascular smooth muscle cells, and its depletion results in decreased cell proliferation and increased apoptosis. A target gene for miR21 in vascular smooth muscle cells is tropomyosin 1.
Forced expression of miR-23a, miR-23b, miR-24, miR-195 and miR-214 results in a potent hypertrophic growth of cardiac cells in vitro, whereas overexpression of miR-150 or miR-181b causes a reduction in cardiomyocyte cell size. Downregulation of miR-133 and its role in cardiac hypertrophy represents one of the most significant findings in miRNA research related to cardiovascular disease.
miRNAs in skin and wound healing
E-cadherin is best characterized as an adhesion junction molecule, which contributes to the maintenance of the epithelial barrier function through homotypic interactions. miRNA-200 and miRNA-205 are highly expressed in normal skin with a positive regulation of E-cadherine, therefore they are essential in maintaining epithelial stability.
miRNAs also play a role in regulating skin pigmentation. Melanin (responsible for pigment) is synthesized at the bottom of the epidermis and found in different locations of the body. Regulation of gene expression linked to skin color has been attributed to miRNA-25, while miRNA-434-5p is implicated in skin whitening and lightening by targeting hyaluronidase and tyrosinase genes.
miRNAs are increasingly becoming important as key contributors in wound healing. miRNA-210 influences keratinocyte proliferation and wound closure, while miRNA-29a directly regulates collagen expression at the posttranscriptional level. Further studies that directly address the role of microRNAs in angiogenesis and wound healing are needed.