These latest findings, which appear in the journal Cell, focus on two microRNAs: miR-143 and miR-145. While there is extensive literature implicating these microRNAs in colon cancer, little is known about their natural function in the colon. So Dr. Guanglu Shi, postdoctoral researcher in Molecular Biology, and other researchers began their five-year investigation by removing or "knocking out" the gene that produces these two microRNAs in mouse models.
The researchers found that the cells that normally increase their growth to make repairs, called epithelial cells, fail under stress in the knockout animals. Epithelial cells line the intestines where food is digested, separating the contents from the rest of the body and absorbing needed nutrients.
"The epithelial cells of the colon normally proliferate quickly to fill in the wounds from an injury. Without these microRNAs, the epithelial cells are unable to switch into this repair mode, so they never heal the wounds and the mice are not able to survive," Dr. Shi said.
In addition, the research upended traditional thinking about where the tiny microRNAs reside, discovering to everyone's surprise that they reside in supporting cells, called mesenchymal cells, instead of the epithelial cells themselves as previously thought.
"This was surprising because colon cancers derive from the epithelial cells, so it was assumed that the microRNAs must function within them," Dr. Mendell said. "If these microRNAs do participate in colon cancer, they must do so by acting from outside the epithelium."
Identifying the accurate location of t
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UT Southwestern Medical Center