MOSCOW, June 25, Vladislav Strekopytov. Scientists have found that cancer is not always associated with hereditary or external factors. It turns out that healthy cells can be reborn due to the attachment of circular RNAs, a recently discovered family of genetic molecules, to DNA.
Program failure
The genetic information that an organism uses as instructions for functioning and development is embedded in the DNA structure. Its fragments, genes, are the natural code for the synthesis of various proteins, each of which performs a specific job.
The signals sent by genes determine the rate of cell growth, their rate of division and life span. Cancer is an abnormal, uncontrolled growth of cells that is triggered when certain genes change and produce the wrong proteins.
The most common cause of cancer is acquired mutations that are not passed from parents to children, but occur during life. The process begins with changing genes in a single cell in a particular organ, such as the breast or colon. The altered genes send a signal to the cell to start an accelerated multiple division. This leads to the formation of a tumor. html» data->
«Cancer» genes
Gene mutations are common. Biologists have calculated that about 500 bases are damaged daily in the DNA chain of each human cell only under the influence of oxidizing compounds. Not all changes are critical, most do not affect health in any way.
According to various estimates, from five to twenty percent of oncological diseases are associated with hereditary changes in genes. In most cases, cancer cells are formed due to acquired (or somatic) mutations. As we age, the body corrects them worse and worse, so older people, whose DNA changes accumulate over many years, get cancer more often than younger people.
In addition to aging, viruses, tobacco use, exposure to certain hormones and toxins, ultraviolet and radioactive radiation. » data-crop-width=»600″ data-crop-height=»600″ data-source-sid=»» class=»lazyload» lazy=»1″ />
The degree of risk also depends on the specialization of genes. Among them are the so-called oncogenes, mutations in which can quickly turn a healthy cell into a cancerous one. The two most famous are HER2, found in breast and ovarian tumors, and RAS, which is responsible for the production of proteins that help cells communicate with each other, grow normally, and die when needed.
Genes that restrict cell growth are called suppressors. Breakdowns in them also lead to uncontrolled growth of cells, which can eventually form a tumor. The most common suppressor gene is p53, or TP53. More than half of cancer patients have it missing or damaged.
Hereditary mutations in the p53 gene are rare, unlike the other two suppressor genes, BRCA1 and BRCA2. Changes in them are inherited and lead to the development of cancer of the breast, ovaries, pancreas and prostate.
DNA repair genes are also at risk. They are designed to correct errors in the copying of genetic information that occurs in the process of division. Mutations in them lead to the accumulation of errors in DNA, which can also cause cancer.
Incorrect assembly
Not so long ago, in human cells, biologists discovered a new family of macromolecules involved in the regulation and expression of genes — circular RNA. Scientists have noticed that the appearance of a large amount of these compounds in the blood plasma is often associated with the development of cancer. More than twenty circular RNAs are now used as tumor markers for the early detection of various types of cancer: colon, ovary, bladder, breast, liver, stomach, kidney and prostate. However, what role they play in the formation of tumors was still unknown.
Australian researchers at Flinders University in Adelaide have solved this mystery by discovering that specific circular RNAs can attach to DNA and cause mutations that lead to cancer. The authors called this process «endogenous RNA-directed DNA damage».
«External environmental and genetic factors have long been considered the primary causes of cancer,» study leader Professor Simon Conn, who heads the CircRNA Laboratory at the Flinders University Institute for Medical Research, said in a press release. «This is the first example of a macromolecule present in many of us that capable of altering DNA and causing cancer from the inside.»
The authors found that cRNAs can bind to DNA in a variety of places using four different mechanisms. As a result, changes occur in the genetic chain, culminating in its break. In order to survive, the cell starts the DNA repair mechanism, but this process is not always perfect. crop-ratio=»1″ data-crop-width=»600″ data-crop-height=»600″ data-source-sid=»rian_infographics» class=»lazyload» lazy=»1″ />
«Due to the fact that cRNAs can change the physical arrangement of broken DNA fragments in the cell nucleus, when glued together, like pieces of a torn book are put together, «page numbering» errors can occur,» explains Professor Conn.
It is known that this process of misassembly of genetic material, called chromosomal translocation, can turn a normal cell into a cancerous one.
Currently, in the medical literature there are about 500 descriptions of chromosomal rearrangements resulting from translocation gene fusions specific for various oncological diseases. Doctors around the world use them to determine the type and stage of cancer and select treatment options. How these mutations arise is only now known.
Philadelphia chromosome
The most famous example of DNA translocation rearrangement is the emergence of the so-called Philadelphia chromosome. This mutation causes up to 95 percent of cases of chronic myeloid leukemia and is found in virtually all patients with B-cell acute lymphoblastic leukemia.
The Philadelphia chromosome, which even has its own designation Ph in the International Cytogenetic Nomenclature, is formed when the ABL1 gene, located on the ninth chromosome, combines with the BCR region of chromosome 22. The new chimeric BCR-ABL protein is constantly active and provokes uncontrolled cell division.
Explorers from Flinders University demonstrated on two types of cells that oncogenic mutations occur when circular RNAs are exposed to known «hot spots» of the genetic chain. Experiments on mice confirmed that the introduction of certain compounds from this group into the blood leads to the rapid development of aggressive leukemia.
After analyzing the database of neonatal blood tests, the authors found that in newborns with acute leukemia, even before the onset of symptoms, the level of specific circular RNA was significantly higher than in the control group.
According to scientists, there is evidence that the process of endogenous RNA-directed DNA damage can lead not only to leukemia, but also to other oncological diseases. And the abundance of circular RNA molecules in cells serves as a reliable criterion for detecting cancer at the earliest stages, when the likelihood of a cure is much higher.