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Cancer causer? Mice that overproduce microRNAs form larger tumors (left, in green) than mice that without extra microRNAs (right).

Small RNAs Tied to Cancer

Tiny RNA molecules may be key players in cancer, according to three reports published in the 9 June Nature. Some versions of these so-called microRNAs can turn cells cancerous, while others appear to keep the disease at bay.

To understand how cells multiply out of control and form tumors, scientists have long focused on proteins that regulate cell growth. But another type of molecule is muscling its way into the field. Called microRNAs, these short bits of RNA about 20 to 25 bases long, have the ability to prevent proteins from being made from messenger RNA (mRNA) (ScienceNOW, 19 December 2002) and are known to be involved in cell growth. Because proteins that are involved in cell growth also have a role in cancer, three groups of researchers decided to see what microRNAs were doing in cancerous tissues.

Cancer biologist Todd Golub at Harvard Medical School in Boston, Massachusetts, and colleagues developed a way to identify small RNAs from more 200 cancer types and found that different types of cancer harbor different subsets of microRNAs. In addition, the microRNAs present in healthy tissue differed markedly from those in tumors. This suggests to the researchers that oncologists might be able to determine a cancer's origin based on the microRNAs present.

Another group, led by molecular biologist Gregory Hannon of Cold Spring Harbor Laboratory, New York, knew that a set of seven microRNAs showed up in some immune system tumors. When the researchers introduced these microRNAs into mice prone to B-cell lymphoma, tumors formed far faster, and the mice died from their cancers earlier than those without the molecules. This indicated that these particular microRNAs could exacerbate uncontrolled cell growth and might be somehow involved in immune system cancers.

A third team, led by molecular geneticist Joshua Mendell at Johns Hopkins University School of Medicine in Baltimore, Maryland, wondered if the same set of seven microRNAs could turn other cancer-promoting genes on or off. The researchers found that overproducing the microRNAs in cultured cells cut down the concentration of E2F1, a protein involved in a cancer growth pathway, suggesting that, in healthy cells, the microRNAs keep cell growth in check.

"All of these [studies] are pretty important for cancer research," says cancer geneticist Paul Meltzer of the National Human Genome Research Institute in Bethesda, Maryland. They show that microRNAs have big roles in cancer, he says, though it's not yet clear what that role is.

Related sites
Golub's lab
Gregory Hannon's lab
Joshua Mendell's lab