Researchers Discover MicroRNA Suppresses p63 Protein

Mar 12, 2008 | Contact Author | By: Katie Schaefer
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Title: Researchers Discover MicroRNA Suppresses p63 Protein
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Researchers at Rockefeller University have discovered a tiny RNA molecule that helps create the protective barrier between the inner layer of skin and the surface of skin. According to the researchers, the results provide insight into both how skin first evolved and how healthy cells can turn cancerous.

Hundreds of these tiny RNA molecules, called microRNAs, are expressed in skin. According to the research, microRNA-203 was of particular interest to them. The interest stemmed from the rapid expression of microRNA-203 during embryo development.  

The researchers found that during the 13th day of development, mice's skin is primarily composed of undifferentiated stem cells. Two days later, these stem cells exit the inner layer of the skin and begin to differentiate into cells that form the outermost, protective layer.

MicroRNA-203’s expression skyrockets precisely during this period, suggesting that it plays some key role in the barrier’s development. MicroRNA-203 helps build a tough protective barrier in the outer layer of the skin by repressing the activity of a molecule called p63. When microRNA-203 can’t stem p63’s activity, cells proliferate.

The researchers are focused on pinpointing where microRNA-203 is expressed. While other microRNAs are specific to heart, muscle and brain tissues, microRNA-203 was found only in the outer layers of stratified epithelial tissues. Although the researchers were studying the skin tissues of mice, this expression pattern is identical to the skin tissues found in humans, zebrafish, chickens and other vertebrates. Researchers hypothesized that the presence of the expression pattern in several species for many years meant that it played a key role.

A genetic technique was then used to express microRNA in the inner layer of the skin, where stem cells proliferate at a fast clip. In a second set of experiments, microRNA-203 was blocked from functioning in the outer layer using an antagomir, a molecule that binds directly to microRNA-203 and shuts down its ability to carry out its function.

Researchers found that the stem cells proliferated significantly less than they did when microRNA-203 was not expressed. As a result, the mice formed very thin skin. Also, the stem cells lost their ability to proliferate, not because microRNA-203 killed them off but because it suppressed the activity of p63.

It was uncovered that the cells in the outer layer proliferated significantly more than they did when microRNA-203 was expressed. This was due to microRNA-203's ability to stop the translation of p63. Therefore, proliferating stem cells within the innermost layer of the epidermis and terminally differentiating cells swiftly transition as they exit this layer and move outward to the skin surface.

The researchers' findings may mean something to cancer research, as p63 is found in excess in cancer cells. The next step will examine whether low expression of microRNA-203 is associated with squamous cell carcinomas and whether by putting back microRNA-203, growth of these cancer cells can be inhibited.