A MicroRNA Regulates the Activity of the p53 Tumor Suppressor Gene

Cancer researchers have discovered a type of microRNA (miRNA) that controls the activity of the p53 tumor-suppressor gene.

In a normal cell p53 is inactivated by its negative regulator, mdm2. When DNA damage or some other forms of stress occur, various pathways lead to the dissociation of the p53 and mdm2 complex. Once activated, p53 will either induce a cell cycle arrest to facilitate repair and survival of the cell or apoptosis to allow the damaged cell to die. While p53 acts to suppress tumor formation, the failure of p53 gene to function correctly has been estimated to lead to more than 50% of cancerous tumors.

Investigators at the Massachusetts Institute of Technology (Cambridge, MA, USA) and the National University of Singapore worked with a zebrafish model that allowed them to examine which molecules modulated the activity of p53. They reported in the March 17, 2009, online edition of the journal Genes and Development that a microRNA labeled miR-125b was a bona fide negative regulator of p53 in both zebrafish and humans.

Their results showed that a reduction in the amount of miRNA125b in the zebrafish cells caused an increase in the level of p53 and of the number of cells undergoing apoptosis. In contrast, an increase in miRNA125b levels decreased the amount of p53 and the number of apoptotic cells.

"Taking all of this data together, the p53 pathway is a major target of miRNA125b," said contributing author Dr. Harvey Lodish, professor of biology and bioengineering at the Massachusetts Institute of Technology. "Most miRNAs have multiple targets, but there are a few cases that a miRNA has one major target and this is one of them."

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Massachusetts Institute of Technology
National University of Singapore