BOSTON, Sept. 29, 2011 /PRNewswire-USNewswire/ -- A pathway activated in cancer plays an unexpected key role in metabolic diseases like type 2 diabetes, according to a study by researchers at Children's Hospital Boston. Evidence that the Lin28/let-7 pathway influences the cellular response to glucose provides a unifying theme to perplexing data that associates human genetic variation with diabetes risk.
The multi-institutional research team led by George Q. Daley, MD, PhD, director of Stem Cell Transplantation and a leader in the Stem Cell Research Program at Children's Hospital Boston – reported their findings in the September 30 issue of the journal Cell.
Let-7 is a microRNA, a small RNA that dampens the expression of a large set of genes related to cell growth and development. Previously, the Daley lab reported that Lin28, an RNA-binding protein found at high levels in the embryo, blocks let-7 production and is aberrantly expressed in about 15% of all cancers.
"The relationship between Lin28 and let-7 is ancient, found in organisms as diverse as worms, mice, and humans," said Daley, a professor of biological chemistry and molecular pharmacology at Harvard Medical School and a Howard Hughes Medical Institute investigator. "This suggested to us that the Lin28/let-7 pathway was profoundly important, but we didn't expect such exciting results."
In the current study, Daley and his team, led by Hao Zhu and Ng Shyh-Chang, set out to study cancer by developing a trio of mouse models with altered expression of Lin28 and let-7. What they discovered, instead, were profound effects on glucose metabolism. When fed a high-fat diet, normal mice develop obesity and diabetes, but mice engineered to express surplus Lin28 remained lean and processed glucose efficiently while mice engineered to express surplus let-7 became diabetic even on a normal diet.
"The results were startling," said Daley. "Previously we had considered these
|SOURCE Children's Hospital Boston|
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