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Regulatory molecule for tumor formation or suppression identified by Singapore, US researchers

MicroRNA targets P53 tumor suppresssor gene

One of the small regulatory molecules, named microRNA-125b, is a novel regulator of p53, an important protein that safeguards cells against cancers, Singapore and U.S. scientists report in the March 17, 2009 issue of the journal Genes & Development.

The scientists found that during embryonic development, this microRNA keeps the level of p53 low to avoid excessive cell death.

But, if the DNA is damaged, the microRNA level is reduced to allow an increase in p53, which eliminates damaged cells and thus prevents tumor formation.

The research was conducted with zebrafish.

"Interestingly, this microRNA is elevated in many types of human cancers, suggesting that it may contribute to the formation of tumours by suppressing the p53 protein," said Bing Lim, M.D., Ph.D., lead author and senior group leader at the Genome Institute of Singapore (GIS), a research institute under the Agency for Science, Technology and Research (A*STAR).

"Hence, our findings have important implications in the diagnosis and treatment of cancers," he added. "The significance of this finding, of course, once again emphasizes the relevance and importance of research linking microRNAs to many subspecialties of human medicine, including cancer and regenerative medicine."

Harvard Medical School's Judy Lieberman, M.D., Ph.D., said, "This important study provides an elegant and beautifully worked out example of the role of microRNAs in master-minding how a cell responds to environmental cues and developmental signals.

"The implication of this study is that these small molecules might be mimicked or antagonized as drugs to treat serious diseases for which no effective treatment exists at present," added Dr. Lieberman, senior investigator at the Immune Disease Institute, and Professor of Pediatrics and Director of the Division of AIDS at Harvard. She is not a co-author of the paper.

Professor of Cell Biology at the Harvard Medical School, Frank McKeon, Ph.D., commented, "This is an elegant use of zebrafish models to uncover how a single microRNA can regulate the p53 tumor suppressor gene. The strength of this regulation suggests that we will hear more about the microRNA-125b in specific human cancers in the near future." Dr. McKeon also is not a co-author of the paper

MicroRNA-125b is a member of the microRNA family of small regulatory molecules that have evolved in nature to regulate tightly the quantity of protein produced by each messenger RNA (mRNA), which generates the group of proteins that determine the unique characteristics of every cell type.

MicroRNAs play complex roles in the simultaneous fine-tuning of many genes in each cell – a role not yet well understood by biologists. It is a complicated, delicate balance that can be profoundly disturbed if just a few microRNAs go awry.

Recent research reveals that microRNAs are abundant in the cell, and that they play important roles in development and in many diseases.

In addition to GIS, the institutes involved in this research work include Singapore's Institute of Molecular and Cell Biology, also a part of A*STAR; the Singapore-MIT Alliance in Singapore; and the Massachusetts Institute of Technology, Harvard Medical School, and Whitehead Institute for Biomedical Research in the US.

The research findings are in the March 17, 2009 online issue of Genes & Development in an article titled, "MicroRNA-125b is a novel negative regulator of p53."

Authors: Minh T. N. Le1,2, Cathleen Teh3,#, Ng Shyh-Chang2,#, Huangming Xie1,2,4, Beiyan Zhou4, Vladimir Korzh3, Harvey F. Lodish1,4,5, Bing Lim1,2,6,*

1. Computation and Systems Biology , Singapore -MIT Alliance , 4 Engineering Drive 3, Singapore 117576

2. Stem Cell and Developmental Biology, Genome Institute of Singapore , 60 Biopolis Street , Genome , Singapore 138672

3. Fish Developmental Biology, Institute of Molecular and Cell Biology, 61 Biopolis Drive , Proteos , Singapore 138673

4. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Suite 601 , Cambridge , MA 02142 , USA

5. Department of Biology, Massachusetts Institute of Technology , Cambridge , MA 02142 , USA

6. CLS 442 Beth Israel Deaconess Medical Center , Harvard Medical School , 300 Brookline Ave, Boston , MA 02215 , USA

# These authors contributed equally to this paper as co-second authors.

Genome Institute of Singapore

The Genome Institute of Singapore (GIS) is a member of the Agency for Science, Technology and Research (A*STAR). It is a national initiative with a global vision that seeks to use genomic sciences to improve public health and public prosperity. Established in 2001 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards the goal of individualized medicine. The key research areas at the GIS include Systems Biology, Stem Cell & Developmental Biology, Cancer Biology & Pharmacology, Human Genetics, Infectious Diseases, Genomic Technologies, and Computational & Mathematical Biology. The genomics infrastructure at the GIS is utilized to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

Agency for Science, Technology and Research (A*STAR):

A*STAR is Singapore 's lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore . A*STAR actively nurtures public sector research and development in Biomedical Sciences, Physical Sciences and Engineering, with a particular focus on fields essential to Singapore's manufacturing industry and new growth industries. It oversees 22 research institutes, consortia and centres, and supports extramural research with the universities, hospital research centres and other local and international partners. At the heart of this knowledge intensive work is human capital. Top local and international scientific talent drive knowledge creation at A*STAR research institutes. The agency also sends scholars for undergraduate, graduate and post-doctoral training in the best universities, a reflection of the high priority A*STAR places on nurturing the next generation of scientific talent.

For more information:
Genome Institute of Singapore
Winnie Serah Lim
Corporate Communications
Tel: (65) 6478 8013
(65) 9730 7884

Cathy Yarbrough | EurekAlert!
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