How Gut Inflammation Triggers Colon Cancer; Key Role of microRNA-34a Determined

Chronic inflammation in the gut increases the risk of colon cancer by as much as 500 percent, and now Duke University researchers think they know why. Their new study points to a biomarker in the cellular machinery that could not only serve as an early warning of colon cancer, but potentially be harnessed to counteract advanced forms of the disease, the second-largest cause of cancer death in the U.S. In the study, published online on February 4, 2016 in the journal Cell Stem Cell, Duke biomedical engineers show how colon cancer development is intricately 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, Ph.D., Associate Professor of Biomedical Engineering at 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 Cancer Stem Cell article is titled “A miR-34a-Numb Feed-Forward Loop Triggered by Inflammation Regulates Asymmetric Stem Cell Division in Intestine and Colon Cancer." In the study, Dr. 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. While researchers knew that miR-34a is responsible for this ability, nobody knew where the ability came from, because normal, healthy colon stem cells don't asymmetrically divide and don't need this microRNA. They wondered if there was a mutation unique to cancer stem cells, or a hidden role for the microRNA in normal physiology. To find out, Dr. Shen and his colleagues deleted miR-34a from the genetic code of some mice. But nothing happened. "It really puzzled the scientific community," said Dr. Shen.
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