UNAB Scientists Discover How to Dismantle a Key RNA in Stomach and Breast Cancer Cells

Inside our cells are RNA molecules that, in addition to performing normal functions, can also help cancer develop and progress. One of the most widely studied is MALAT1, an RNA molecule that functions like an engine, helping tumor cells survive and multiply more rapidly.

However, a team from the Institute of Biomedical Sciences at Universidad Andrés Bello, led by researcher Rodrigo Aguilar, identified a potential vulnerability in this molecule. Using laboratory models of stomach and breast cancer, they were able to completely dismantle it by removing just a tiny fragment of its structure.

Meticulous Work

To accomplish this, the team used CRISPR-Cas9, the technology known as «molecular scissors» that enables precise editing of genetic material. Unlike previous studies, which had examined this region of MALAT1 only in test tubes, the UNAB team made the cut directly in living cells.

«We removed the fragment in living cells and discovered that, by taking out this tiny piece, the entire MALAT1 molecule broke down and lost its function. This demonstrates that this small segment is a structural pillar that holds this cancer-associated RNA together.»

The scale of the finding becomes clearer through a comparison offered by Aguilar himself.

«If we imagined that MALAT1 RNA were a giant word made up of 7,400 letters, we used the CRISPR scissors to remove only 10 to 40 of those letters. We expected to see some effect, but not for such a tiny alteration to cause the entire molecule to collapse,» he said.

According to Aguilar, this was one of the study’s most unexpected findings and led him to describe this small region as MALAT1’s «Achilles’ heel.»

Cancer Cells Stopped Multiplying and Began to Die

The effect was not limited to the RNA itself. Once this piece was removed, the edited cancer cells showed a dramatic change in behavior.

«First, we saw that the cancer cells lost their ability to divide rapidly,» Aguilar explained.

The team then used a flow cytometer, specialized equipment at the Institute that makes it possible to analyze cells individually, to confirm that the effect went beyond slowing their growth.

«We demonstrated that the cells had not only stopped multiplying, but were also dying at a much higher rate compared with cells that had not been modified. By removing this key piece, we left them unprotected,» the researcher explained.

From the Laboratory to a Potential Treatment

Although the study was conducted using laboratory models, its findings could contribute to the development of future treatments. Aguilar explained that research groups around the world are already working on drugs designed to block the same region of MALAT1 that his team removed.

«What our study provides is biological evidence that targeting this precise site in living cells is effective. Our results provide the scientific support needed for the biomedical industry to continue advancing the development of drugs or gene therapies directed at this target.»

However, the path toward a treatment available to patients remains a long one. According to Aguilar, before clinical trials in humans can be considered, the strategy must be validated in human tumors and researchers must rule out unwanted effects on healthy tissue.

«This entire process typically takes between five and 10 years, but every finding like ours is an essential step toward closing that gap,» Aguilar said.

A Collaborative Effort in Chile and Abroad

Aguilar emphasized that the advance was not the work of a single laboratory.

«This advance was made possible through collaboration among three research groups at UNAB’s Institute of Biomedical Sciences, a team from the University of Chile, and the valuable contributions of colleagues in Spain and the United States, together with the tremendous dedication of our students,» he said.

For Aguilar, the results also carry significance beyond the scientific findings themselves.

«It is concrete proof that we can produce internationally impactful research in Chile when we combine our capabilities and work as a team,» he concluded.