Summary of Scientists Identify One of the Causes of Aggressive Liver Cancer – A “Molecular Staple”:
Researchers have uncovered a novel DNA repair mechanism that impedes cancer treatment, according to a recent study. The use of error correction mechanisms is essential for cells, but inducing errors can kill cancer cells. In radiotherapy and chemotherapy, cancer cells’ DNA is damaged to cause cellular defects, but some tumors have highly effective DNA repair systems that allow them to evade these treatments. Researchers have observed a molecular staple in action using nanotechnology, which helps with repairing damaged DNA. Understanding this mechanism may help with the development of strategies to counteract liver cancers. The long RNA molecule NIHCOLE binds broken DNA fragments together, obstructing the efficacy of radiotherapy.
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As humans, we rely on our cells to function properly in order for us to live healthy lives. However, sometimes these cells experience malfunctions that can lead to problems in the body, including cancer. Most treatments for cancer involve inducing cellular defects to kill off the cancer cells, but some tumor cells have an exceptional DNA repair system that allows them to escape treatment. A recent study has shed light on one of these extraordinary DNA repair systems, which could lead to new approaches for cancer therapies.
Features of the DNA Repair System
The study, published in Cell Reports, describes a molecular staple that is part of the DNA repair system. Researchers used a nanotechnology method to observe this molecular staple in action for the first time. The team, led by Óscar Llorca from CNIO, Fernando Moreno-Herrero from CNB, and Puri Fortes from CIMA-University of Navarra, discovered that NIHCOLE, an RNA molecule found mainly in the most aggressive tumors, is very effective at repairing broken DNA. NIHCOLE forms a bridge that binds the broken DNA fragments together, allowing them to survive and evade treatment.
The researchers used magnetic tweezers, a nanotechnology technique, to study the physical properties of individual molecules. They designed a DNA molecule that mimics broken DNA and attached a tiny magnetic bead to one end of it. Using magnetic nano-tweezers, they were able to detect the junction between the two fragmented ends of the DNA. By pulling on one end of the DNA, they were able to determine whether it was a reconstituted DNA molecule in which the broken ends had been joined together or still broken. These data showed that NIHCOLE confers advantages on tumor cells by helping them to repair DNA breaks.
Relevance to Treating Liver Cancer
The study has significant implications for liver cancer, which is the most common cancer worldwide. Puri Fortes’ team previously discovered that half of patients with liver cancer produce NIHCOLE, which is associated with a poor prognosis. Understanding how NIHCOLE works may help in the development of strategies to combat liver cancers with the worst prognosis. The researchers suggest that the use of NIHCOLE inhibitor drugs may represent a new therapy for the most common form of liver cancer.
Conclusion
The discovery of this exceptional DNA repair system sheds light on how cancer cells can evade treatment and provides new possibilities for developing cancer therapies. NIHCOLE, previously considered part of “junk DNA,” is one of many long RNA molecules that have been discovered to have a prevalent function in cancer, even though their existence and function have only recently been discovered. The study provides insights into how cancer cells repair their DNA and survive, suggesting a possible approach for developing new cancer therapies.
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