Dark Matter of the genome hid cancer treatment: what scientists found

Dark Matter of the genome hid cancer treatment: what scientists found

Cancer is the second most important cause of death in Switzerland, one of the most dangerous of the various types of cancers is lung cancer, which kills most patients and remains largely incurable. Unfortunately, even recently approved treatments can last only a few months; few survive in the long term at the metastasis stage, so scientists are actively seeking new treatments.

Dark Matter of the genome — What is it?

As new targets, they used an unexplored class of genes — a long, uncoded RNA or dnRNA.

Long, non-coded RNAs exist in abundance in the so-called "dark matter" genome. That part of the DNA that does not encode the protein and makes up the vast majority of it. The gene contains about 20,000 "classical" genes that encode the proteins. But this number is negligible against the background of 100,000 dnRNA. The biological functions of 99% dnRNA are unknown.

According to their name "long non-coded RNA", unlike matrix RNAs, dnRNA does not encode protein plans. As with mRNA, the instructions for building dnRNA are contained in cell DNA.

Preparation for the experiment

In order to study the role of dnRNA in NMRC, researchers examined publicly available data sets, resulting in more than 800 dnRNAs, the importance of which for cancer cells biologists wanted to test, for which they developed a special screening system that prevents the production of selected dnRNs by removing part of their building instructions from the DNA itself.

Scientists have already applied the screening system to two NMRS cell lines from patients, and then have seen how the inhibition of the selected dnRNs affects the characteristics of cancer cells, including behavior that contributes to the progress of the disease: proliferation, metastasis formation and resistance to therapy.

As a result, of the 800 candidates studied, biologists have compiled a list of only 80 dnRNAs with a high degree of reliability, which are important to the NMRD, and of these 80 scientists have chosen only a few for subsequent experiments.

How was the study?

For subsequent experiments, biologists have used an approach that does not work at the DNA level, namely, that of dnRNA after its formation. To this end, scientists have used small chemically synthesized RNAs, which are anti-intellectual oligonucleotides. They are associated with the target and cause degradation of the dnRNA. It should be noted that several ADFs have already been approved for the treatment of human diseases, but not yet for the treatment of cancer.

What did the experiment show?

Subsequent experiments have shown that for most of the selected dnRNA, their destruction through ADF inhibits the division of cancer cells in a cell culture. It is important to note that the same treatment has had little effect on the pulmonary cells that should not be harmed by cancer treatment. In the 3D models of the NMRD, which resembled more of a tumor than a cell culture, the inhibition of one dnRNA using ADF has reduced the growth of the tumor by more than half.

According to the authors of the study, they were "pretty surprised to see how well anti-intellectual oligonucleotides inhibit the growth of tumors in different models".

What's next?

Researchers are continuing research on pre-clinical cancer models and are considering collaborating with existing companies or establishing a startup to develop a drug for patient treatment.

With regard to other types of cancer, scientists have stated that their approach should be easily adapted to identify new potential treatments for other types of cancer. The next target is colorctal cancer. It is the world's third largest malignant neoplasm every year, with about 880,000 deaths worldwide, with about 1.8 million new cases diagnosed annually. This is an important goal.