Anti-cancer RNA triplets
Brain-destroying disease gives birth to a cure for cancer
Neurodegenerative diseases destroy the nervous system, for which they got their name. One of them, Huntington's disease, occurs due to the repeated repetition in the huntingtin gene of a sequence of three nucleotides – cytosine (C), adenine (A) and guanine (G) – triplet CAG. The longer the chain of such triplets, the faster the nerve cells are destroyed, which means that the symptoms of the disease appear earlier – a violation of mental functions and the appearance of uncontrolled movements, and its course is heavier.
DNA is a "recipe" for building a protein using RNA molecules. RNA reads the code from DNA, and then collects protein from amino acids based on it. However, RNAs themselves can block protein production at an intermediate stage: after reading the gene code from DNA and before assembling amino acids into a protein strand. It was previously shown that this is why short RNA chains consisting of CAG repeats in Huntington's syndrome and CAG repeats (Y is uracil) in the case of muscle hypotension syndrome are toxic to cells.
At the same time, patients suffering from these syndromes had an unusually low susceptibility to cancer. The researchers decided to check whether the repeats of triplets in DNA, as well as the short RNAs generated by them, are the cause of patients' resistance to cancer.
For the experiment, the scientists constructed a dimer molecule from two RNA chains, one of which contained CAG repeats, and the second contained TSUG, that is, exactly those triplets that caused neurodegenerative disorders. When scientists injected this dimer into various lines of mouse and human cancer cells, their growth stopped after a few hours, and later most of the cells died. The researchers compared the toxicity of small RNAs carrying CAG/TSUG repeats with the effect on cancer cells of trinucleotide repeats causing other diseases, as well as with the deadly effect of artificially constructed triplets.
It turned out that the toxicity of repeats of different triplets strongly depends on the order in which they are located, although which nucleotides are included in them also matters. The most toxic, that is, causing the death of the largest number of cancer cells, was a group of triplets, which included combinations of CAG and CSG, and the toxicity was conservative – independent of tissue, cell line, species.
Scientists have suggested that trinucleotide repeats accumulate when correcting errors in the functioning of DNA. When a lot of mistakes occur in a cell, the repetitions form too long a chain and the body gets rid of the cell. The reverse side of this useful mechanism, developed by evolution, are diseases when defective DNA is inherited.
The introduction of an RNA dimer to mice slowed down the growth of a cancerous tumor, but had no harmful effect on the general well-being and the condition of other mouse tissues, since healthy cells show resistance to such short-term effects. Thus, the found short RNA can become a new weapon against cancer.
The study is published in the journal EMBO Reports (Murmann et al., Small interfering RNAs based on huntingtin trinucleotide repeats are highly toxic to cancer cells).
Portal "Eternal youth" http://vechnayamolodost.ru