Cancer link: microRNA grabs the spotlight.
These findings suggest that microRNA plays a major role in regulating gene activation, says Scott M. Hammond of the University of North Carolina at Chapel Hill, an investigator on one of the studies.
In a third report, scientists show how patterns of activity in the genes that encode microRNA reveal signatures that doctors might someday use to identify a tumor's origin.
"These three new studies change the landscape of cancer genetics," says Paul S. Meltzer of the National Human Genome Research Institute in Bethesda, Md. The studies appear in the June 9 Nature.
Scientists estimate that more than 22,000 genes encode human proteins. When activated, these genes transcribe their DNA onto genetic strands called messenger RNA. These strands serve as templates for protein assembly on cellular organelles known as ribosomes.
In contrast, only a few hundred genes carry the DNA blueprints for microRNA (SN: 1/12/02, p. 24). RNA molecules transcribed from these genes don't get translated into protein. Instead, they fold back upon themselves, yielding microRNA.
Hammond and his colleagues demonstrated the potential role of microRNA molecules in cancer by performing experiments using mice genetically engineered to make excess c-myc--a protein implicated in several cancers, including lymphoma. The team engineered half the mice to also produce a surplus of certain types of microRNA abundant in lymphoma cells.
Most of the mice with excess c-myc, but not extra microRNA, survived beyond 100 days. However, all the mice with the extra c-myc and microRNA, developed lymphoma within about 50 days and died 2 weeks later, Hammond's team reports.
In another study, Joshua T. Mendell of Johns Hopkins Medical Institutions in Baltimore and his colleagues considered the same types of microRNA. The team demonstrated that two of these microRNAs inhibit a protein called E2F1, which regulates cell proliferation.
Meltzer says that microRNA might be exerting its effects by binding to messenger RNA before it can be translated into proteins that would switch genes on or off.
MicroRNA's mechanism of action "is still pretty murky," Mendell notes.
In the third study, scientists measured activity among 217 genes encoding microRNA molecules. By comparing healthy cells and cancerous cells, the scientists discerned patterns of gene activation that can distinguish many cancers, reports a team led by Todd R. Golub of the Dana-Farber Cancer Institute and the Howard Hughes Medical Institute in Boston.
"It's entirely possible that these microRNA signatures might help us [classify cancers] because they seem to be so tissue-specific," says Meltzer. By knowing which tissue spawned a cancer that has spread from its original site, doctors can choose the best treatment for it, he says.
Some benefits of microRNA profiling are already showing up, says Carlos M. Croce of Ohio State University in Columbus. Last year, he and his colleagues found that the technique could reveal whether patients with chronic lymphocytic leukemia had a slow-growing or an aggressive cancer.
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|Title Annotation:||This Week|
|Date:||Jun 11, 2005|
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