Ural Federal University: Scientists Identified a Gene Mechanism Suspending the Development of a Malignant Brain Tumor

Scientists in Ekaterinburg have discovered that the Klotho gene is able to suppress the growth of glioblastoma cells, a malignant tumor of the brain and spinal cord. The experiments contribute to the development of new methods of diagnosing and treating glioblastoma and were carried out with the support of the Ministry of Health of the Russian Federation. An article describing the studies and their results was published in the Journal of Molecular Neuroscience.

When active, the Klotho gene (Klotho is the goddess of destiny in ancient Greek mythology) produces two forms of the protein (it is also named after the goddess Klotho) – a longer transmembrane form and a truncated secreted form. The transmembrane form of the protein is embedded in the membrane of the individual cell and affects it directly. The secreted form is released by the cell into the intercellular space, enters the bloodstream and spreads throughout the body, affecting many, including distant cells.

“World science already had evidence that the Klotho gene can suppress glioblastoma cell viability. The uniqueness of our studies is that they were conducted specifically on the secreted form of the Klotho protein. This methodological nuance allows us to take a slightly broader look at the mechanisms of tumor disease development,” says Vsevolod Melekhin, head of the research group, associate professor at the Ural Federal University, an employee of the Ural State Medical University and the Institute of Medical Cell Technology.

In their experiments, Ekaterinburg scientists used the Klotho gene built into a plasmid, a closed-ring DNA molecule taken from bacteria. Along with it, the gene was implanted into glioblastoma cells. The plasmid cannot enter the cell on its own, for which the researchers used a complex of positively charged DNA-lipids: they are readily attracted to the negatively charged cell surface, fuse with the cell membrane, which also consists mainly of lipids, and pass through it into the cell.

“It is easier to deliver a gene with viral constructs, which easily penetrate the cell. But viruses have the ability to embed themselves in the genome, the totality of the cell’s hereditary material. And the use of technologies that involve tampering with the genome is restricted by law and ethical standards. The plasmid only works inside the cell for two to three weeks, and then it is destroyed, leaving no trace in the cell’s genome,” explains Vsevolod Melekhin.

Placed inside glioblastoma cells and in a state of hyperactivity, the Klotho gene produced a secreted protein of the same name, which entered the intercellular space. After conducting three tests, scientists recorded that after 72 hours the protein production increased almost 15-fold, the viability of glioblastoma cells dropped by 8%, the number of cells decreased by almost 20% of the control values.

“The body gets rid of unwanted or damaged, mutated cells with the help of apoptosis, a mechanism that triggers the program of self-destruction, “suicide” of cells. In malignant tumor cells, the apoptosis mechanism is blocked, so they multiply constantly and uncontrollably. However, as a result of our experiment, we registered a significant increase in the number of apoptotic cells,” Melekhin adds.

According to the scientist, the research conducted on the secreted form of the Klotho protein is another step toward creating more effective treatment and diagnostic approaches.

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