Overexpression of the Polycomb repressive complex 2 (PRC2) subunit Enhancer of Zeste 2 (EZH2) occurs in several malignancies, including prostate cancer, breast cancer, medulloblastoma, and glioblastoma multiforme.
Taken together, our study reports EZH2 as a transcriptional activator, a key target of which is AR, and suggests a drug-combinatory approach to treat advanced prostate cancer.
Gene expression profiling indicates that mouse tumors resemble human prostate cancer neuroendocrine variants; both mouse and human tumors exhibit increased expression of epigenetic reprogramming factors such as Ezh2 and Sox2.
When these results are considered together with published data on EZH2 and on the E2F3 control protein pRB, we conclude that the pRB-E2F3-EZH2 control axis may have a critical role in modulating aggressiveness of individual human prostate cancer.
The Polycomb Group Protein EZH2 is a transcriptional repressor involved in controlling cellular memory and has been linked to aggressive prostate cancer.
While the test for the prostate cancer antigen 3 (PCA3) is commercially available, the aim of our research was to test other putative urine markers in multiplex settings (AMACR (α-methylacyl-CoA racemase), EZH2 (enhancer of zeste homolog 2), GOLM1 (golgi membrane protein 1), MSMB (microseminoprotein, β), SPINK1 (serine peptidase inhibitor) and TRPM8 (transient receptor potential cation channel, subfamily M, member 8)).
Thus, dysregulated expression of EZH2 may be involved in the progression of prostate cancer, as well as being a marker that distinguishes indolent prostate cancer from those at risk of lethal progression.
The present findings suggest, at least in part, that miR-26a induced by an AHCY inhibitor can regulate oncogenic EZH2 expression, and could thus be an important mechanism of action for AHCY inhibitors in the treatment of prostate cancer.
EZH2 is also implicated in EMT activation, and its up-regulation represents one of the most frequent epigenetic alterations during prostate cancer progression.
EZH2 has strong prognostic impact in prostate cancer and might contribute to the development of a fraction of genetically instable and particularly aggressive prostate cancers.
Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase polycomb group (PcG) protein, which has been implicated in the process of cellular differentiation and cancer progression for both breast and prostate cancer.
Increased expression of the transcriptional repressor EZH2 has been reported to be associated with poor prognosis in various malignancies including breast cancer and prostate cancer.
Here, we have shown that hypoxia leads to increased expression of VEGF, IL-6, and CSC marker genes such as Nanog, Oct4 and EZH2, and also increased the expression of miR-21, an oncogenic miRNA, in prostate cancer (PCa) cells (PC-3 and LNCaP).
Overexpression of the polycomb group protein enhancer of zeste homologue 2 (EZH2) occurs in diverse malignancies, including prostate cancer, breast cancer, and glioblastoma multiforme (GBM).