Enhancer of zeste homolog 2 (EZH2), is a histone methyltransferase involved in epigenetic silencing of target genes and plays a central role in regulating embryonic stem cells, metastasis, and cancer survival. EZH2 is overexpressed in aggressive solid tumors and has been shown to function as an oncogene, however, the mechanism of its elevation in cancer is unclear. Here, we identified that a microRNA is a tumor suppressor that inhibits EZH2 expression and function. In contrast to EZH2, this microRNA expression is decreased during prostate cancer progression. Importantly, the genomic loci of this microRNA are somatically lost in prostate cancer as well as in other cancers. Taken together, this suggests a model in which genomic loss of a microRNA in cancer leads to overexpression of EZH2 and concomitant dysregulation of epigenetic pathways resulting in cancer progression and metastasis.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B90.
- American Association for Cancer Research