The three miR-34 genes expressed in p53 carrying mice silence other cell proliferation genes.
Researchers at Cold Spring Harbor Laboratory, Howard Hughes Medical Institute, and Applied Biosystems (ABI) discovered that a family of miRNAs are components in the p53 pathway, which stops the growth of tumor cells in mice.
The team of scientists performed gene expression profiling experiments that identified three miRNA genes in the miR-34 family as candidate tumor suppressor genes using ABI’s TaqMan® MicroRNA Assays.
A study from McKusick-Nathans Institute of Genetic Medicine published in the June 8 issue of Molecular Cell specifically implicated miR-34a in in p53’s mechanism of action in colon cancer.
The current research, which will be published in the June 28th issue of Nature, showed that in mouse tumor cells that contained a functioning p53 gene, expression levels of the three miR-34 genes increased compared to levels of the miRNAs in cells without the p53 gene. The resulting miR-34 miRNAs then repressed the expression of other genes related to cell growth, suggesting that one way that p53 may suppress tumor growth is by inducing the expression of miR-34 genes, which then silence expression of various cell proliferation genes.
Consistent with their finding in mice tissue samples, the researchers also found comparatively low levels of miR-34s in human tumors and cancer cell lines.