Researchers from Duke University think they have discovered why chronic gut inflammation increases the risk of colon cancer by up to 500%. The team identified a biomarker in the cellular machinery that could serve as an early warning sign of colon cancer and potentially be utilized to treat the advanced stage of the disease. The results of the study were published in the journal Cell Stem Cell.
“A quarter of the world’s population is affected by some type of gut inflammation,” explained Xiling Shen, lead author of the paper from Duke University. “These patients always have a much higher chance of developing colon cancer, but it was never clear why. Now we have found a link.”
The main focus of the study was miR-34a – a microRNA that enables cancer stem cells to divide asymmetrically, a process that controls the cancerous stem cell population.
The involvement of miR-34a in colon cancer was known by researchers, but its source remained to be identified. To address this question, the team removed miR-34a from the genetic code of mice. However, the deletion did not produce any effect, which puzzled the scientific community.
In the latest study, miR-34a was deleted from mice with inflamed tissues, which led to tumor development. The researchers concluded that miR-34a is triggered to act when the gut becomes inflamed, leading to the asymmetrical division and the promotion of normal stem cell populations.
In the early stages of tumor growth, miR-34a stays active to regulate the stem cell population. As the cancer progresses, it develops mutations that suppress miR-34a production, giving the cells the ability to change back into stem cells, a process that makes late-stage cancers difficult to treat.
“Typically when you look at tumors and see something that isn’t in normal tissue, you think it’s a bad thing,” commented 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 you silence them in late-stage cancer, it’s like the supervillain carried off the superhero and the cancer becomes much worse.”
Researchers could utilize miR-34a levels to test for early-stage cancers, when they are easiest to treat. In addition, as a possible treatment for late-stage cancer, researchers want to get increase miR-34a expression in cancer cells. Clinical trials are currently in progress in multiple types of cancer, but this is the first study showing that this strategy might also work in colon cancer.