( ognize. It turns out that in the...)MicroRNA helps prevent tumors

It turns out that in the non-protein-producing region, Hmga2 has seven sites that are complementary to the let-7 microRNA, a microRNA expressed in the later stages of animal development. Mayr wondered whether loss of these let-7 binding sites, and therefore loss of regulation by let-7 of Hmga2, might cause over-expression of Hmga2 that in turn would result in tumor formation.

To find out, Mayr created a series of Hmga2 in which various numbers of let-7 sites were destroyed. She found clear evidence that when exposed to let-7, the fewer sites that were intact, the more protein was produced.

Next, she tested whether disrupting let-7's ability to repress Hmga2 would lead toward tumor creation. In a standard in vitro test of cancer-causing genes, colonies of mouse cells that expressed normal or shortened Hmga2 did not grow significantly, while cells in which Hmga2 contained disrupted let-7 sites did. In fact, the more that let-7 sites were damaged, the greater the number of colonies.

Mayr also worked with MIT assistant professor Michael Hemann to inject these cells in mice with a compromised immune system. The scientists found that the mice with cells that expressed the version of Hmga2 with the disrupted let-7 sites developed tumors.

Overall, the results highlight a new mechanism for cancer formation. Hmga2, and perhaps certain other genes that are normally regulated by microRNAs, can help give rise to tumors if a mutation in the gene disrupts the microRNA's ability to regulate it. In addition, the results show that the interaction of one microRNA with one of its target genes can produce a certain trait in mammals. This is important because scientists are only beginning to learn the functions of microRNAs in animals.

"Because hundreds of human genes appear to be regulated by the let-7 microRNA, we were afraid we wouldn't see any difference when we changed only one of these target genes," says Dav
'"/>

Source:Whitehead Institute for Biomedical Research