Micro-RNAs, Diseases and Therapy: What are MicroRNAs and How are They Related to Cancer and Stem Cells

Besides mediating between the DNA and proteins, RNA has a function in regulating the levels of proteins in the cell. This regulation is critical for the cell’s behavior.

The central dogma of biology declares that segments of the DNA, referred to as genes, are transcribed into RNA molecules, each representing a copy of the gene and finally the RNA is translated to an active protein which usually has a mechanical or structural role in the cell. In the past it was common knowledge that RNA merely mediates between the genetic code and the function it encodes to in the form of proteins. However, as early as 1961 the famous researchers Jacob and Monod suggested that since an RNA molecule is capable of binding another RNA molecule, the two can interact in a way that will change the stability of or the rate of protein production from one of them. This hypothesis was found to be true several years ago in all kingdoms of life as the regulatory RNAs were discovered.

The History of Regulatory RNAs

The first example of an RNA that alters the translation rate of another RNA into protein was found in the well-explored bacterium E. coli in 1972. Twenty one years after, a regulatory RNA was found in the worm C. elegans. This RNA was only 22 nucleotides long and in a mysterious way it led to a decrease in the number of proteins synthesized from two other RNAs. In 2000 another short RNA was found to control the translation rate of several genes and it became clear that a new family of RNA, conserved in higher eukaryotes, has been discovered, the microRNAs.

What Are MicroRNAs?

MicroRNAs (miRNAs or miRs) are short segments of RNA in a length of about 20–22 nucleotides. They are processed from a longer precursor and require several proteins in order to exert their function. The exact mechanism in which miRs are acting is not fully understood, however, we do know that they directly bind their targets mRNAs leading to a decrease or full stop of protein synthesis from that target. The miRNAs can be thought of as the brakes of the protein synthesis machinery of the cell. They can abruptly and instantly prevent certain protein from being produced.

MiRNAs are related, among others, to cell differentiation, development, proliferation and apoptosis (cell death). It has been recently shown that certain miRs are highly expressed in one tissue but not in the others. The miRs, in this view, are used to keep the levels of proteins not needed in that certain tissue very low. It is also known that some miRNAs are differentially expressed throughout development and their expression is altered through the different stages of cell differentiation. This mechanism takes advantage of the short time it takes miRs to close down the production of their targets to rapidly change the protein content of the cell.

The Role of miRNAs in Disease and Therapy

Cancer is caused by cells proliferating when inappropriate. Whether cancer cells are generated from stem cells or from normal cells that have regenerated the ability to proliferate, the decision-making of the cell whether to proliferate or die is malfunctioning. MiRNAs are key players in each of the processes. Because of their ability to quickly alter the synthesis of specific proteins they are most suitable for this type of regulation. It was indeed shown that in several cancer cells some miRNA levels are changed and, more interestingly, when the missing miRNA is introduced to the cancer cells they stop proliferating. MiRNAs, hence, are leader players in both formation and therapy of cancer.

Inducing reverse differentiation from a sorted cell back into a stem cell is also beneficial and can be used in treating a wide variety of situations from cancer to cardiovascular arrest, diabetes and more. Today, scientists are able to transform a somatic cell into a stem cell by inserting new genes into its genome, a process reaching its goal with limited success. Changing the amount of certain miRNAs instead, could lead to the same results scientists believe, but with a higher success rate.

The world of RNA, previously thought of as a mediator between the genetic code and the proteins it encodes for was found in recent years to play a major role in the tight regulation of the cell’s designation. Incorrect amounts of miRNAs can lead to cancer and other diseases, however, reassessing their correct amount can reverse the process and lead to a healthy cell. MiRNAs can also be used to regenerate stem cells and help cure other diseases as well but more research is due before this goal is reached.

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