What makes some tumors as gentle as purring kittens and others of the same cancer type as ferocious as saber-toothed tigers? A miRNA (miR-101) was recently shown to take a bite out of cancer by inhibiting the EZH2 histone methyltransferase.
The study by Arul Chinnaiyan and co-workers at the University of Michigan Medical School, the National Cancer Centre (Singapore), and the Genome Institute of Singapore appeared in a recent issue of Science.EZH2 tri-methylates histone H3 at lysine 27 (H3K27) to silence target genes.
Overexpression of the histone methyltransferase, which occurs in aggressive subsets of many solid tumors, promotes tumor growth and metastasis, but the mechanism behind EZH2 elevation was unknown. Chinnaiyan and colleagues found that miR-101 binds within the EZH2 3’UTR to attenuate the protein’s expression. Interestingly, high rates of genomic loss of miR-101 were observed in metastatic prostate cancer and several other solid tumors, and the loss of miR-101 correlated with EZH2 overexpression.
MiR-101 overexpression decreased global tri-methyl H3K27 levels and increased the expression of EZH2 target genes. Furthermore, the overexpression of miR-101 in cancer cells with elevated EZH2 levels reduced cell proliferation, migration, and xenograft growth. The investigators say that the re-introduction of miR-101 to aggressive tumors could be a useful therapeutic approach.
Get all the details at Science, November 2008.