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Lost Molecule is Lethal for Liver Cancer Cells in Mice
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Lost Molecule is Lethal for Liver Cancer Cells in Mice

Lost Molecule is Lethal for Liver Cancer Cells in Mice
News

Lost Molecule is Lethal for Liver Cancer Cells in Mice

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Scientists at Johns Hopkins have discovered a potential strategy for cancer therapy by focusing on what’s missing in tumors.

Noticing the conspicuous absence of single-stranded genetic snippets called microRNAs in cancer cells, a team of researchers from Johns Hopkins and Nationwide Children’s Hospital delivered these tiny regulators of genes to mice with liver cancer and found that tumor cells rapidly died while healthy cells remained unaffected.

Publishing results of the study June 12 in Cell, the researchers say they have provided one of the first demonstrations that microRNA replacement provides an effective therapy in an animal model of human disease.

“This work suggests that microRNA replacement may be a highly effective and nontoxic treatment strategy for some cancers or even other diseases,” says Josh Mendell, M.D., Ph.D., an associate professor in the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine. “We set out to learn whether tumors in a mouse model of liver cancer had reduced levels of specific microRNAs and to determine the effects of restoring normal levels of these microRNAs to these cancer cells. We were very excited to see that the tumors were, in fact, very vulnerable to microRNA replacement.”

His team had considered the possibility that the replacement of a single small RNA might have little if any effect, especially in the setting of all the complex changes that drive the aberrant behavior of a cancer cell. But the tumor cells in the mouse were indeed sensitive to the restoration of the microRNA—so much so that they died, rapidly.

“This concept of replacing microRNAs that are expressed in high levels in normal tissues but lost in diseases hasn’t been explored before,” Mendell says. “Our work raises the possibility of a more general therapeutic approach that is based on restoring microRNAs to diseased tissues.”

The Hopkins team was building on precedent-setting research (published January 2008 in Nature Genetics) showing that in a Petri dish, replacing microRNAs in lymphoma cells stopped the formation of tumors when the cells were injected into mice.

The new study involves animals that develop liver tumors closely resembling the human disease. Researchers chose to target the liver because, according to Mendell, it is a large organ whose function is detoxification and therefore, is a relatively accessible target for the delivery of small molecules, compared to other tissues.

Origianl Research Article: Kota et al Therapeutic microRNA Delivery Suppresses Tumorigenesis in a Murine Liver Cancer Model.  Cell, Volume 137, Issue 6, 1005-1017, 12 June 2009 

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