Abstract
MicroRNAs (miRNAs) are short, noncoding RNAs that posttranscriptionally regulate gene expression. Over 300 miRNA genes have been identified in the human genome. We have undertaken the study of miRNA function in mammals. Using a custom microarray platform, we investigated miRNA expression patterns in mammalian development and in cancer. We found that many miRNAs are downregulated in cancer. On the other hand, several miRNA genes are overexpressed in tumor cell lines and primary tumors. Seven of these cancer-associated miRNAs are clustered in a single primary transcript termed chr13orf 25 or OncomiR-1. This cluster is located in a region amplified in lymphoma and several solid malignancies. Ectopic expression of these miRNAs in a mouse model of lymphoma accelerated disease progression. In addition, the lymphomas had reduced apoptosis and were more disseminated into secondary regions. This work establishes noncoding RNAs, and specifically miRNAs, as oncogenes in human cancers.
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Acknowledgments
The author thanks the following for their contributions to the work described in this paper: Mike Thomson, Summer Goodson, Keith Woods, Marty Newman, Handan Kaygun, Jerry Bernards, Emily Kuty, Chuck Perou, Joel Parker, Gerry Usary, Jason Leib, Cheol-koo Lee, Rene Ketting, Ronald Plasterk, Jack Keene, Patrick Lager, Haifan Lin, Greg Hannon, Lin He, Jidong Lu, Michelle Carmell, David Mu, Scott Powers, Carlos Cordon-Cardo, Scott Lowe, Mike Hemann, Yue Xiong, Antonio Giraldez, Paul Barnes, Tom Maynard, and UNC Microarray Facility. Software was kindly provided by Michael Eisen. Support from the Department of Cell and Developmental Biology, General Motors Cancer Research Foundation, and NIH-NIGMS also made this work possible.