microRNA-203 – protection against skin cancer
In humans, about 30,000 cells of the surface protective layer of the skin die every minute. Their place is taken by cells migrating from deeper layers and forming a dense protective barrier. Under the influence of physical and chemical environmental factors, mutations often occur in skin cells, and in order to prevent their transmission to the next generations of cells in animals, a mechanism for suppressing the proliferation of cells of the surface layers of the skin using specific microRNAs appeared in the process of evolution.
The data obtained by scientists at Rockefeller University not only shed light on the processes of skin formation, but also reveal possible mechanisms of malignancy of healthy cells.
Hundreds of different microRNAs are expressed in skin cells, but one of them, microRNA–203, attracted the authors' special attention. During the development of the embryo, the expression of microRNA-203 increases dramatically at the same time. microRNA-203, which is practically not registered on day 13, becomes the predominant microRNA of skin cells within two days.
The authors found that on the 13th day of intrauterine development, the skin of mice mainly consists of undifferentiated stem cells. Two days later, these cells leave the deep layers of the skin and begin to differentiate into cells that form the surface protective layer of the skin. A sharp increase in the expression of microRNA-203 during this period indicates the important role of this molecule in the development of the skin barrier.
Analysis of various tissues showed that microRNA-203 is expressed exclusively in the cells of the upper layers of a specific type of skin – the multilayer epithelium. Moreover, it turned out that the microRNA-203 expression profile is identical for humans, striped danio (zebra fish), chickens and other species, i.e. for vertebrates, between the appearance of which more than 400 million years have passed during the evolutionary process.
To find out the functions of microRNA-203, the authors conducted two series of experiments. In the first series, they caused premature expression of microRNA-203 in rapidly proliferating cells of the upper layer of the skin using a genetic technique, and in the second series, they blocked the functioning of microRNA–203 using a compound that specifically binds to it.
In the first case, stem cells proliferated much more slowly, which led to the formation of very thin skin that does not perform a protective function. The authors explain this effect by the fact that microRNA-203 suppresses the activity of the p63 protein, whose function is to maintain cell proliferation, primarily stem cells. In the second case, the cells of the upper layers of the skin proliferated significantly more actively than the same cells expressing microRNA-203. The reason for this was the absence of free microRNA-203 molecules in the cell, suppressing the functioning of the p63 protein.
The researchers found that microRNA-203 stops the translation of the p63 protein, resulting in the rapid transformation of proliferating stem cells of the deep layers of the epidermis into terminally differentiated cells and their movement into the surface layers of the skin.
The importance of this discovery is also due to the fact that a high level of p63 protein is characteristic of malignant cells. The next stage of the work, the authors plan to analyze the expression of microRNA-203 in squamous cell skin cancer cells and the possibility of stopping tumor growth by increasing the expression of this molecule.