Scientists in Singapore and the US have recently found that a microRNA, named microRNA-125b, is a novel regulator of p53, an important protein that safeguards cells against cancers. The research finding was reported on March 17, 2009 in the prestigious journal, Genes & Development.
The unique characteristics of every cell type are determined by a group of proteins produced in the cell by molecules known as messenger RNAs (mRNAs). The quantity of protein produced by each mRNA must therefore be tightly regulated, and several mechanisms had evolved in nature to do this. An ancient mechanism, common to plants and animals, involve a family of small regulatory molecules known as microRNAs.
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.
During embryonic development, this microRNA keeps the level of p53 low to avoid excessive cell death. On the other hand, if a DNA is damaged, the microRNA level is reduced to allow an increase in p53, which eliminates damaged cells and thus prevents tumour formation.
Dr Bing Lim, 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), said, "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. Hence, our findings have important implications in the diagnosis and treatment of cancers. 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."
Dr Judy Lieberman, senior investigator at the Immune Disease Institute, and professor of Paediatrics and director of the Division of AIDS at the Harvard Medical School added, "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 results will be useful to develop treatment for serious diseases for which no effective treatment exists at present.
Professor of Cell Biology at the Harvard Medical School, Dr Frank McKeon added, "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."
The institutes involved in this research work were the GIS, Institute of Molecular and Cell Biology, and Singapore-MIT Alliance in Singapore; and the Massachusetts Institute of Technology, Harvard Medical School, and Whitehead Institute for Biomedical Research in the US.
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.
A*STAR is Singapore's lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore.