Scientists have identified a new group of culprits that plays a major role in the development of human cancers.
They are tiny bits of ribonucleic acid (RNA) called microRNAs that control gene activity. In particular, they stop or slow the production of cellular messengers necessary for division and growth, researchers said in four studies, three of which will appear in today's edition of Nature. The fourth study, which centres on stem cells, will appear in a later issue.
The findings suggest an expanded role in human development and disease for RNA interference, a process of genetic regulation used by cells to either destroy messages sent by genes or stop targeted genes from functioning. The studies shed greater light on how the process of cell growth goes awry in cancer, said Paul Meltzer, a researcher at the National Human Genome Research Institute in Bethesda, Md.
"It's a new way of looking at cancer," Dr. Meltzer, who wrote an accompanying editorial on the studies for the journal, said in a telephone interview. "It's a new way of looking at important aspects of biology in general."
Companies such as Cambridge, Massachusetts-based Alnylam Pharmaceuticals and Boulder, Colorado-based Sirna Therapeutics are developing drugs and treatments based on RNA interference.
Until recently, scientists had believed that microRNAs played a limited role in cells' lives, Dr. Meltzer said. A study led by Jun Lu, a cancer researcher at the Harvard University and Massachusetts Institute of Technology-affiliated Broad Institute in Cambridge suggests that microRNAs may play a key role in controlling cancer cell growth.
Levels of microRNAs were lower in cancer cells than in normal tissues, the study said. The researchers also found patterns in the microRNA levels that suggest they could be used to classify cancers with unclear diagnoses.
"It could be particularly useful in cancers that have spread from other tissues and the original cancer can't be found," Dr. Meltzer said.
MicroRNAs interact with the Myc gene, an important cell-growth regulator that appears to be abnormal in as many as half of all tumours, according to researchers led by Kathryn O'Donnell, a cancer researcher at Johns Hopkins University School of Medicine in Baltimore. In normal tissues, Myc prompts production of microRNAs that appear to keep those growth processes in check by influencing another gene called E2F, said Josh Mendell, a Johns Hopkins geneticist who co-wrote the study.
"MicroRNAs could act as the brakes on potential tumour-accelerating processes," he said in a telephone interview.
Researchers led by Lin He of Cold Spring Harbor Laboratory in New York found a cluster of microRNA-producing genes in a DNA segment known to be associated with a blood cancer called B-cell lymphoma. The findings suggest for the first time that a malfunction in microRNAs may be the cause of a specific cancer, the study said.
"This is a new class of genes to be linked to cancer," said Gregory Hannon, a Cold Spring Harbor molecular biologist who helped write the study. "We're finding that these are a major class of regulatory molecules."
Researchers found further evidence of the critical role for microRNAs and RNA interference in their control over division of stem cells, which can develop into a wide variety of cell types and tissues. MicroRNAs appear to allow stem cells to continue dividing while mature cells around them are kept from growing, said Hannele Ruohola-Baker, a University of Washington biochemist in Seattle who co-wrote the stem-cell study.
"A key question in stem-cell biology is how they get past the signals that tell cells to stop dividing," she said in a telephone interview.
Further investigation may show whether microRNAs control both cancer and stem cells through the same pathways, Dr. Ruohola-Baker said. "That would be very exciting."