Replacing microRNA may offer new possibilities for cancer treatment: study in mice shows liver tumors shrunk or didn't develop.

It's a simple idea: Treat cancer by finding out what's missing from a cancer cell and replacing it.

Experiments in mice suggest that inserting one small missing molecule could fight cancer without harming normal tissue, researchers at Johns Hopkins University in Baltimore and the Nationwide Children's Hospital in Columbus, Ohio, report in a study in the June 12 Cell.

The molecule in this case is a small RNA chain known as a microRNA. MicroRNAs (abbreviated as miRNks) are involved in a wide range of body processes including cellular differentiation and tissue growth. They run about 22 bases long, but their small size belies their influence--they help regulate hundreds or thousands of genes.

In the past decade, certain types of miRNA have been shown to be made at lower-than-normal levels in cancer cells. Scientists have previously explored the idea that replacing the missing miRNAs might reverse the cancer, but not in a way that could lead to viable treatments, said Joshua Mendell of Johns Hopkins, one of the study's authors.

"One of the things that distinguishes this work is that we used a clinically relevant delivery vehicle to replace a microRNA that's missing," Mendell says. The team used a harmless virus that acts as a sort of mail carrier to deliver miRNA to cancer cells.

The researchers worked with mice that develop tumors similar to those in human liver cancer. Most of the untreated mice developed cancers that nearly consumed their livers. But eight out of 10 mice receiving the miRNA had small liver tumors or none at all.

"It's door-opening research" that will encourage others to move into the field, says George Calin of the University of Texas M.D. Anderson Cancer Center in Houston.

Mendell and his colleagues focused on a particular miRNA called miR-26a, chosen because it was much less abundant in liver cancer cells than in normal liver cells. "We thought that the tumor cells might be sensitive to the miRNA" but that the normal parts of the liver would not be harmed, Mendell says. Restoring the miR-26a stopped the cancerous cells from creating two molecules called cyclins that are used in cell replication, effectively preventing the cells from multiplying.

"Although microRNAs have been shown to play an important role in cancer pathogenesis, not too many reports have shown that altering a single microRNA can suppress cancer development in vivo," comments Baohong Zhang of East Carolina University in Greenville, N.C. "This result has opened a novel strategy for cancer therapy."

The study has practical benefit, Calin says, because it shows potential for treating a specific type of cancer called hepatocellular carcinoma, which accounts for 80 to 90 percent of liver cancers.

Calin also says that this research suggests it may be possible to use different miRNAs as therapies for many diseases, not just cancers. MicroRNAs have a wide variety of functions, and some have been linked with autoimmune disorders, diabetes and heart disease.