Over the past few years, scientists have discovered that a new class of genetic regulators called "microRNAs" influences normal human growth and development. Now, researchers have found that microRNAs also play an important role in human cancer. The findings are published in tomorrow's issue of the journal Nature (June 9).
"These studies change the landscape of cancer genetics by establishing the specific microRNAs expressed in most common cancers and investigating the effects of microRNAs on cancer development and cancer genes," says cancer expert Dr. Paul Meltzer, who did not participate in the studies.
In one of the new studies, researchers at Cold Spring Harbor Laboratory, led by Dr. Gregory Hannon, and at the University of North Carolina, Chapel Hill, led by Dr. Scott Hammond, focused on a segment of human chromosome 13 that was known to be amplified (i.e. present in excess) in several tumor types including B-cell lymphoma. The researchers observed that this DNA segment, referred to as the mir-17-92 cluster, has the potential to encode seven microRNAs.
To determine whether excess expression of microRNAs encoded by the mir-17-92 cluster might be involved in cancer, the scientists first examined whether one or more of the microRNAs was expressed at abnormally high levels in four B-cell lymphoma cell lines in which the mir-17-92 cluster was amplified, compared to normal B-cells and to five leukemia and lymphoma cell lines in which the mir-17-92 cluster was not amplified.
The researchers found that indeed, five microRNAs encoded by the mir-17-92 cluster were overexpressed specifically in the B-cell lymphoma cell lines bearing an amplified mir-17-92 cluster.
Next, the scientists examined the expression levels of the mir-17-92 microRNAs in human tumor biopsies including 46 lymphomas and 47 colorectal carcinomas. They observed significant (greater than fivefold) overexpression of the mir-17-92 microRNAs in 65% of the lymphomas, with an average mir-17-92 microRNA overexpression of 10-fold in those lymphomas (and a high of 82-fold microRNA overexpression). In contrast, 15% of the colorectal carcinomas displayed greater than fivefold mir-17-92 microRNA overexpression.
These findings suggested that mir-17-92 microRNA overexpression might contribute to human cancer, particularly to B-cell lymphoma but also to other forms of the disease.