MADRID, 28 Dic. (EUROPA PRESS) –
Scientists at the Cold Spring Harbor Laboratory (CSHL) in the United States have discovered a fragment of gene regulatory RNA that may contribute to the spread of many breast cancers. In animal experiments, the researchers were able to reduce the growth of metastatic tumors with a molecule designed to attack that RNA and trigger its destruction. The same strategy could be used to develop a new breast cancer treatment for patients.
The study, led by CSHL Professor and Research Director David Spector, is published in the journal Nature Communications. In 2016, Spector and his colleagues identified dozens of RNA molecules that were more prevalent in breast cancer cells than in non-cancer cells of the same type.
All were long non-coding RNAs (lncRNAs): RNA molecules that do not code for proteins and are believed to perform various regulatory functions within cells. The current study investigated how one of these, RNA 25 associated with mammary tumors (MaTAR 25), affected the behavior of breast cancer cells in mice.
Experiments by Kung-Chi Chang, a graduate student in Spector’s lab, indicate that the molecule contributes to cancer progression in several ways, accelerating the growth of cells and their ability to migrate and invade tissues.
These effects may be due to changes in the activity of the tensin1 gene, which the team found to be one of the targets of MaTAR 25. Tensin1 helps connect a cell’s inner cytoskeleton to the outer matrix that surrounds it, and thus, it is positioned to influence the movement of a cell as well as its growth regulation pathways.
To remove MaTAR 25, the researchers designed a small piece of nucleic acid that recognizes and binds to its sequence. Once attached, that molecule, known as an antisense oligonucleotide, alerts an enzyme within cells to destroy lncRNA. When the researchers injected this molecule into the bloodstream of mice, it reached tumor cells and degraded most of the MaTAR 25, with dramatic effects.
“When we did the histology of the tumors we discovered that they were very necrotic, which means that there was a lot of cell death after this RNA was degraded,” Spector recalls. “And obviously, that is an important finding, but still, if not more importantly, we found a very significant reduction in metastasis to the lungs. So this really gave us very interesting data that this RNA molecule has some potential as a therapeutic target. “
Spector’s team discovered that high levels of an RNA analog called LINC01271 are associated with more aggressive disease in patients’ breast tumors. They are now investigating whether an antisense oligonucleotide that targets LINC01271 can interfere with tumor growth and metastasis in patient-derived models of breast cancer.
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