The latest research, to be published in the June 28 issue of Nature, identified three miRNA molecules that form an important part of the p53 tumour suppressor network and may suggest new approaches for the treatment of various cancers.
The p53 tumour suppressor gene has previously been shown to be functionally impaired in more than 60 per cent of human cancers and has become known as 'the guardian of the genome' for the role it plays in conserving genetic stability.
The US researchers discovered the three miRNA genes, called miR-34s, by studying their relative expression levels in mouse tumour cells that contained a functioning p53 gene compared with tumour cells with no p53 function.
"This study marks the first time that researchers have compared expression of miRNAs in cell samples that contain copies of the gene for p53 to expression of miRNA in cells in which the p53 gene copies have been removed," said Dr Caifu Chen, a director of science at Applied Biosystems and a co-author of the study.
"Because of the success of this research, we now know that miRNAs have a tumour suppressor function."
Extensive gene profiling experiments using the TaqMan-based real-time PCR miRNA assay from Applied Biosystems detected significant decreases in the amount of miR-34s in the mice that had no p53 function.
The miR-34s were expressed at levels of less than a few hundred copies per cell, making the sensitivity of the PCR technique essential to the success of the study.
"The sensitivity and dynamic range of the TaqMan miRNA assays made it possible for us to precisely measure the levels of miR-34 genes expressed in cells with and without copies of the p53 gene," said Dr Lin He of Cold Spring Harbor Laboratory and a co-author of the article.
While the researchers are yet to fully elucidate the role that miR-34s play in the p53 tumour suppressor network, they believe that there is great potential for altering miR-34 expression to harness the cancer fighting function of the p53 pathway and could lead to the development of the miR-34s as therapeutic anticancer agents.
"Together, these data identify the miR-34 family of microRNAs as direct targets of p53 that play a key role in the p53 tumour suppressor network," said Dr He.
"Our finding reveals new details about how one of the most important and well-studied tumour suppressor networks prevents cancer formation."
