Duke University researchers found Chronic inflammation in the gut increases the risk of colon cancer by as much as 500 percent. The new study discovers a biomarker in the cellular machinery that could serve as an early warning of colon cancer. Colon cancer is the second-largest cause of cancer death in the U.S.
In the study, published on February 4 in the journal Cell Stem Cell, the Duke study showed how colon cancer development is linked to a specific microRNA that dictates how cells divide.
A quarter of the world's population is affected by some type of gut inflammation," said lead author Xiling Shen, associate professor of biomedical engineering at Duke University. Patients with this condition always have a much higher chance of developing colon cancer, but it was never clear why. Now we have found a link."
In the study, Shen's group focused on a microRNA called miR-34a that gives cancer stem cells the odd ability to divide asymmetrically. This process controls the cancerous stem cell population and generates a diverse set of cells. Researchers knew that miR-34a had the ability to do this, however, it was not known where it came from. Normal, healthy colon stem cells don't asymmetrically divide and don't need microRNA. Researchers wondered if there was a mutation unique to cancer stem cells, or a hidden role for the microRNA in normal physiology.
Shen and his colleagues deleted miR-34a from the genetic code of some mice with no significant finding. It really puzzled the scientific community," said Shen. Usually if something is important and you delete it, it causes a problem."
In the latest study, however, the problem showed up when the mice's tissues became inflamed. Without any microRNA miR-34a, their stem cells quickly grew out of control and formed many tumor-like structures.
Based on the study, Shen's group concluded that even though miR-34a is active in cancer, it's actually a good thing. It is triggered when the gut becomes inflamed, miR-34a forces the process of asymmetrical division, helping to control normal stem cell populations.
It was found that even in early stages of tumor growth, the microRNA remains active to keep the cancer stem cell population down. Unfortunately, as cancer progresses, its cells develop mutations that enable shutting off miR-34a, causing cells to divide into flexible hybrids that can revert back into stem cells if needed. It's this flexibility that makes late-stage cancers so difficult to stop.
Typically when examining tumors and see something that isn't in normal tissue, you think it's a bad thing," said Shen. But it turns out that, under normal circumstances, these microRNAs are the good guys who only show up when things go wrong. And when they are silenced in late-stage cancer, it's like the supervillain carried off the superhero and the cancer becomes much worse."
Shen says understanding the role of miR-34a might lead to this supervillain's vulnerability. With a test to look for elevated levels of miR-34a, researchers could create an early warning system to catch cancers in its beginning stages when they are much easier to cure. As for possible treatment for late-stage cancer, researchers are trying to get the cancer cells to express miR-34a again. This would stop the tumor cells from gaining the flexibility to revert back to stem cells and allow doctors to get the cancer under control.
Clinical trials are currently trying to do just this in multiple cancer types, but this is the first study that has shown that it might also work for colon cancer. Prevention is always the best method and researchers recommend building a healthy immune system in efforts to combat the illness from the start.
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