17 November 2014

Small interfering RNAs against cancer

A well-known oncogene was "silenced"

Copper newsResearchers from the United States have developed a new approach to suppress the KRAS gene, which encodes a protein that stimulates the formation of a malignant tumor.

The results of the study published in the journal Molecular Cancer Therapeutics (Pecot et al., Therapeutic Silencing of KRAS using Systematically Delivered siRNAs) showed that the use of small interfering RNAs (miRNAs) not only dramatically stops the growth of cancer in the cells of the lung and colon, but also prevents the spread of metastases.

The KRAS protein is a signaling molecule that triggers a cascade of reactions that stimulate cell growth and survival. Mutations in this gene lead to their uncontrolled division. KRAS gene mutations occur in about 30 percent of lung, colon, pancreatic and thyroid cancers.

Suppression of the gene responsible for this process is difficult, since there are not enough places to insert small molecules and drug binding substances, and all attempts to inhibit this gene have had limited success. Researchers from the University of North Carolina have tested the possibilities of RNA interference - the process of suppressing gene expression (synthesis of the corresponding protein). This method uses short segments of RNA that cause suppression of the expression of certain genes. These fragments of mRNA bind to the matrix RNA (mRNA) in the cell, which is why the cell begins to perceive the mRNA that reads the information of the KRAS gene as hostile, which leads to its destruction by enzymes. As a result, uncontrolled cell growth stops.

RNA interference has great prospects in the treatment of liver diseases, viral infections and cancer. The scientists selected the most effective miRNA sequences that they tested on the culture of malignant cells. The results showed that these synthetic RNA segments suppressed more than 90 percent of KRAS (matrix RNA) gene production, and also significantly reduced the activity of two signaling molecules (PERK and pMEK), which are also involved in the growth of tumor cells. Then the effect of these miRNAs, hidden in lipid nanoparticles, was tested on mice with a model of lung and colon cancer. The results are similar – the experimental method significantly slowed down the development of primary tumors (by about 70 percent). In addition, suppression of the KRAS gene reduced the spread of metastases to other organs by 80 percent.

On the left is a bioluminescence image of a tumor affected by miRNA that does not suppress KRAS expression in control group mice; on the right is a tumor reduction after the use of a KRAS inhibitor (figure from the press release of the University of North Carolina at Chapel Hill School of Medicine: UNC researchers silence leading cancer–causing gene) – VM.In the future, these data may become a platform for the development of targeted antitumor therapy, but now this is only the first step towards gaining control over this oncogene.

Portal "Eternal youth" http://vechnayamolodost.ru17.11.2014

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