Breast cancer: a new target
Researchers from the Cold Spring Harbor Laboratory have discovered an RNA fragment that probably contributes to the spread of many types of breast cancer. In animal experiments, they were able to reduce the growth of metastatic tumors by using a molecule targeting this RNA. This strategy may form the basis of a new method of treating breast cancer in humans.
In 2016, David Spector and his colleagues identified dozens of RNA molecules that were more common in breast cancer cells than in benign cells of the same type. All of them were long non–coding RNAs (DNRNAS) - RNA molecules that do not encode proteins and are believed to play various regulatory roles inside cells. The new study examined one of the regulatory RNAs associated with breast cancer (Mammary Tumor Associated RNA 25, MaTAR25) and its effect on the behavior of breast cancer cells in mice.
Experiments have shown that MaTAR25 promotes the development of cancer in several ways: it accelerates the growth of cells and their ability to migrate and penetrate into healthy tissues. These effects may be associated with changes in the activity of the tensin 1 gene, which, as it turned out, is one of the goals of MaTAR25. Tensin1 helps to connect the internal cytoskeleton of the cell with its surrounding environment and, therefore, can influence cell movement.
To eliminate MaTAR25, the researchers used a small fragment of nucleic acid (antisense oligonucleotide), which recognizes its sequence and binds to it. After binding, this molecule warns the enzyme inside the cell about the destruction of dnRNA. When the researchers injected the drug molecule into the bloodstream of mice, it reached the tumor cells and destroyed most of MaTAR25 with impressive effects.
On the right: cancer cells are moving, and long rigid actin filaments (marked in green) act as tentacles, helping them to move. The adhesive protein paxillin (red) collects at the edge of the cell, attaching it to the surface. On the left: cells devoid of MaTAR25 are flat. Actin and paxillin filaments are destroyed (specks instead of filaments), so the cells cannot move efficiently, which reduces their ability to metastasize. Source: Kung-Chi Chang/Spector lab.
Histological analysis of tumors after treatment showed the presence of necrosis. This means that the destruction of MaTAR25 triggers the death of cancer cells. In addition, the researchers found a significant reduction in metastases in the lungs of animals. Spector's group found that a high level of similar regulatory RNA LINC01271 in humans is associated with a more aggressive course of breast tumors. They are currently looking for an antisense oligonucleotide targeting LINC01271 to inhibit tumor growth and metastasis in human breast cancer models.
Article by K.Chang et al. MaTAR25 lncRNA Regulates the Tensin1 Gene to Impact Breast Cancer Progression published in the journal Nature Communications.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Cold Spring Harbor Laboratory: Regulatory RNAs promote breast cancer metastasis.