Study establishes new class of cancer-causing genesJune 08, 2005Researchers link aberrant 'microRNA' expression to human cancer 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. To test that idea directly, the researchers examined whether elevated expression of mir-17-92 or other microRNAs could accelerate the onset of cancer and/or decrease survival in a mouse model of B-cell lymphoma. As expected, control animals developed B-cell lymphoma after about 2 months, and the overall survival of this group (n = 12) after 3 months was 75%. In stark contrast, animals in which the mir-17-92 microRNAs were overexpressed experienced accelerated development of B-cell lymphoma (40 days compared to 2 months), and-significantly-none of the animals in this group (n = 14) survived after 3 months, compared to the 75% survival rate of the control animals in which the mir-17-92 microRNAs were not overexpressed. Moreover, tumors induced in mir-17-92 microRNA-overexpressing animals consistently invaded organs outside the lymphoid compartment (including liver, lung, and kidney), and lacked the extensive "programmed cell death" or apoptosis observed in the control tumors and which helps keeps tumors in check. These findings indicate that overexpression of the mir-17-92 microRNAs can contribute to highly malignant tumors. Collectively, the results of the study establish that microRNAs can function as bona fide oncogenes, leading the researchers to propose that such oncogenic microRNAs be designated "oncomiRs," with mir-17-92 being oncomiR-1. A copy of the study and interviews with Dr. Hannon are available on request. Cold Spring Harbor Laboratory | |||||||||||||||||||||
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Related MicroRNA Current Events and MicroRNA News Articles Genetic predictors of esophageal cancer identified Researchers have identified 11 genotypes that may increase esophageal cancer risk, according to research published in the November issue of Cancer Prevention Research, a journal of the American Association for Cancer Research. MicroRNAs make for safer cancer treatments Viruses -- long regarded solely as disease agents -- now are being used in therapies for cancer. Concerns over the safety of these so-called oncolytic viruses stem from their potential to damage healthy tissues. Short RNAs show a long history MicroRNAs, the tiny molecules that fine-tune gene expression, were first discovered in 1993. But it turns out they've been around for a billion years. Tiny molecule helps control blood-vessel development, researchers find The development and repair of heart tissue and blood vessels is intimately tied to a tiny piece of ribonucleic acid (RNA) that is found nowhere else in the body, researchers at UT Southwestern Medical Center have found. Gladstone scientists identify single microRNA that controls blood vessel development Scientists from the Gladstone Institute of Cardiovascular Disease (GICD) and UCSF have identified a key regulatory factor that controls development of the human vascular system, the extensive network of arteries, veins, and capillaries that allow blood to reach all tissues and organs. How to build a plant Walking through a tropical or temperate forest immediately impresses us with the myriad forms and soaring structures of the plant world, but our knowledge of how plants are actually built, cell by cell, is still incomplete. Hebrew University study opening new route for combating viruses A unique technique for analyzing the function of microRNAs developed by a Hebrew University of Jerusalem doctoral student has led to the discovery of a new mechanism by which viruses evade the human immune system. How body size is regulated: International study discovers ten new genes related to human growth Scientists are beginning to unravel the question why people distinctly vary in size. Scientists dig deeper into the genetics of schizophrenia by evaluating microRNAs Researchers at Columbia University Medical Center have illuminated a window into how abnormalities in microRNAs, a family of molecules that regulate expression of numerous genes, may contribute to the behavioral and neuronal deficits associated with schizophrenia and possibly other brain disorders. MicroRNAs appear essential for retinal health Retinas in newborn mice appear perfectly fine without any help from tiny bits of genetic material called microRNAs except for one thing - the retinas do not work. More MicroRNA Current Events and MicroRNA News Articles |
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