It was long believed that environmental and genetic factors are the main causes of cancer. But now researchers have stumbled upon certain molecules that cause cancer from within.
Cancer is a debilitating disease that affected no less than 124,000 Dutch people last year. And the number of diagnoses made each year is increasing. Meanwhile, scientists and doctors have a fairly good idea of the causes of cancer. “It is generally believed that cancer is caused by genetic factors that can be inherited from parents (such as certain mutations in breast or ovarian cancer) or by external environmental factors (such as smoking in lung cancer or ultraviolet light in skin cancer),” explains researcher Simon. Conn talking to Scientias.nl out. But cancer can also arise from within, as he and his colleagues prove in a revolutionary study. And in this case naturally occurring molecules are the culprits.
The molecules in question are a certain type of RNA molecules. There are roughly four different types, but in this case it concerns the so-called ‘circular RNA molecules’. What are those? In the human body, DNA is translated into proteins: the building blocks of our body. But to make a protein from DNA, an intermediate step is needed: the RNA. “RNA is actually a kind of copy of DNA, which allows cells to regulate how much protein is produced,” explains Conn. “To prepare the RNA for translation into a protein, the RNA molecule must first be reduced in size in a process that splicing is called. Splicing is not foolproof and it can cause parts of the RNA to be reassembled in the wrong order. This produces circular RNAs, which, unlike most RNA molecules, have a closed circular structure. This makes them very stable and is therefore rarely translated into proteins.”
Now, of course, the question is how these circular RNA molecules cause cancer. That’s right. In the new study, the researchers found that specific circular RNAs can stick to the DNA in our cells and then cause DNA mutations that result in cancer. “These specific circular RNAs can bind to DNA at many different locations in a range of cells,” Conn says. “By attaching to the DNA at specific sites, these circular RNAs cause a number of changes that ultimately cause the DNA to break. The cell then has to repair this in order to survive.”
However, this repair does not always go smoothly. “It can even result in small mutations, like a misspelled word in a book, or worse, very large and devastating mutations,” Conn continues. “Because the circular RNAs can also change the physical location of the broken DNA in the cell nucleus, two different parts of the DNA can be glued together during the repair process – similar to tearing two different books in half and then glued together . This results in the formation of carcinogenic gene fusions, which transform the cell into a cancer cell.”
With the study, the researchers have shown that a molecule present in many of us causes nasty mutations and thus causes cancer from within. “It is the first time that a molecule produced in our cells has been shown to have the ability to mutate our own DNA,” said Conn. “These molecules are not found in everyone, by the way. However, we often see them in people who are later diagnosed with cancer.”
Fight against cancer
According to the researcher, the findings from the study are very useful in our ongoing fight against cancer. “As mentioned, we often see large amounts of RNA molecules in people who later develop cancer,” says Conn. “This suggests that detecting these molecules and potentially destroying them could prevent cancer. In short, if we detect these molecules in humans, it is likely that we can halt the development of certain cancers – and even other diseases involving circular RNAs.”
The researcher also makes an important comment here. “Destruction of these circular RNAs at an early stage could prevent the development of cancer,” he says. “But it’s probably not possible to cure patients who already have cancer, since the cancer-causing gene fusions have already happened in this case.” However, the new insights can prevent the treatment of one form of cancer from leading to the development of another form. “If we see an increase in the number of circular RNAs during treatment, it may be justified to choose a different chemotherapy to reduce the risk of relapse in cancer patients,” explains Conn. “Therefore, our findings are promising; it can lead to a lower incidence of relapse.”
All in all, the researchers demonstrate the link between a person’s cancer risk and the activity of circular RNAs. They call their revolutionary finding ER3D (short for endogenous RNA-directed DNA damage), establishing an entirely new field of research. “Our study shows that circular RNA molecules, found in all kingdoms of life and serving a variety of functions, can bind to DNA and cause cancer-causing mutations,” Conn summarizes. The findings have been published in the prestigious journal Cancer Cell.
ER3D is not only limited to cancer, but may also play a role in other diseases. The research team is now continuing their promising study to study the role of circular RNAs in cancer as well as these other diseases.
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