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Cancer Link: MicroRNA grabs the spotlight

Nathan Seppa

A type of genetic molecule barely on the radar screen of scientists a decade ago has emerged as a major player in cancer biology. Known as microRNA because they consist of short strands of ribonucleic acid (RNA), these molecules can team with a known cancer-causing protein to accelerate the growth of cancer, one research group reports. Another team has found that some microRNA molecules inhibit a compound that keeps cell replication in check.

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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References:

Calin, G.A. … and C.M. Croce. 2004. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proceedings of the National Academy of Sciences 101(Aug. 10):11755–11760. Abstract .

He, L. … and S.M. Hammond. 2005. A microRNA polycistron as a potential human oncogene. Nature 435(June 9):828–833. Abstract.

Lu, J. … and T.R. Golub. 2005. MicroRNA expression profiles classify human cancers. Nature 435(June 9):834–838. Abstract.

O'Donnell, K.A. … and J.T. Mendell. 2005. c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435(June 9):839–843. Abstract.

Further Readings:

Bartel, D.P. 2004. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 116(Jan. 23):281–297. Abstract.

Calin, G. … and C.M. Croce. 2004. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proceedings of the National Academy of Sciences 101(March 2):2999–3004. Abstract.

Meltzer, P.S. 2005. Small RNAs with big impacts. Nature 435(June 9):745–746.

Ota, A., et al. 2004. Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Research 64:3087–3095. Abstract.

Travis, J. 2003. Human RNA genes counted up. Science News 163(April 5):221. Available at Science News.

______. 2002. Biological dark matter. Science News 161(Jan. 12):24–25. Available at Science News.

Sources:

Carlos M. Croce
Ohio State University
400 West 12th Avenue
385 Wiseman Hall
Columbus, OH 43210

Todd R. Golub
Howard Hughes Medical Institute
Harvard Medical School
Dana-Farber Cancer Institute
44 Binney Street
Boston, MA 02115

Scott M. Hammond
Department of Cell and Developmental Biology
Lineberger Comprehensive Cancer Center
University of North Carolina, Chapel Hill
Chapel Hill, NC 27599

Paul S. Meltzer
Cancer Genetics Branch
National Human Genome Research Institute
Building 49, Room 4A10
49 Convent Drive, MSC 4470
Bethesda, MD 20892-4470

Joshua T. Mendell
Institute of Genetic Medicine
Johns Hopkins University
539 Broadway Research Building
733 N. Broadway
Baltimore, MD 21205


From Science News, Volume 167, No. 24, June 11, 2005, p. 371.