Cancer jigsaw includes tiny genetic molecules
Protein regulators could be used to identify types of tumour.
Scientists have uncovered a surprising role for non-coding genetic material in the development of cancer. The realization should help with both the diagnosis and treatment of tumours.
Cancer biologists have known for decades that some genes cause cancer by creating proteins that disrupt normal cellular growth. Now researchers have found that chunks of genetic material known as microRNAs can trigger tumours by regulating such proteins.
"Everybody has been focused on understanding how proteins fit into cancer-causing pathways, but there is another regulatory pathway that controls not the protein product but its utilization," says Greg Hannon of the Cold Spring Harbor Laboratory in New York.
Scientists have long thought of RNA as the intermediate 'messenger' between genes and proteins, because DNA is transcribed into RNA before being translated into protein.
But during the past few years, scientists have discovered that many genes are transcribed into RNA and never made into proteins. These 'non-coding' RNAs seem to act as regulators rather than messengers. They influence the expression of genes, for instance, by destroying coding RNA molecules so they cannot be translated into proteins.
This process was known to be important in normal human growth and development, but research that appears in Nature this week shows that a type of non-coding RNAs called micro-RNAs can cause disease as well. Hannon's work, for example, shows that some microRNAs can accelerate the development of cancer when transplanted into mice1.
The discovery should also help researchers to identify the type of cancer that an individual has, a step that is crucial in assigning treatment.
Todd Golub's lab at the Dana-Farber Cancer Institute in Boston, Massachusetts, has found that different types of tumour express different levels of microRNAs2. By measuring the levels of expression of 217 genes in different types of cancers, Golub and colleagues made microRNA 'profiles' of many cancers. The researchers showed they could use these profiles to diagnose the origin of tumours that are difficult to classify by the traditional method of looking at cell shape and character under a microscope.
MicroRNA profiling also worked better than existing genetic profiling methods, correctly diagnosing 12 of 17 tricky tumours. The existing method diagnosed only one of these tumours correctly.
Others note that the discovery could have knock-on effects for treatment strategies. "These papers show that microRNAs are potentially therapeutic. You could deliver them to tumours, maybe in combination, or even along with chemotherapeutic drugs," says John Rossi, a molecular biologist at the Beckman Research Institute in Duarte, California. "A lot of people are going to want to follow up on this work."
- He L., et al. Nature, 435. 828 - 833 (2005).
- Lu J., et al. Nature, 435. 834 - 838 (2005).