Epigenetic regulation of cancer progression by EZH2: from biological insights to therapeutic potential

Abstract

Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and a catalytic component of PRC2, catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3) to regulate gene expression through epigenetic machinery. EZH2 also functions both as a transcriptional suppressor and a transcriptional co-activator, depending on H3K27me3 or not and on the different cellular contexts. Unsurprisingly, numerous studies have highlighted the role of EZH2 in cancer development and progression. Through modulating critical gene expression, EZH2 promotes cell survival, proliferation, epithelial to mesenchymal, invasion, and drug resistance of cancer cells. The tumor suppressive effects of EZH2 are also identified. What is more, EZH2 has decisive roles in immune cells (for example, T cells, NK cells, dendritic cells and macrophages), which are essential components in tumor microenvironment. In this review, we aim to discuss the molecular functions of EZH2, highlight recent findings regarding the physiological functions and related regulation of EZH2 in cancer pathogenesis. Furthermore, we summarized and updated the emerging roles of EZH2 in tumor immunity, and current pre-clinical and clinical trials of EZH2 inhibitors in cancer therapy.

Inhibition of EZH2 Ameliorates Lupus‐Like Disease in MRL/lpr Mice

“…EZH2 overexpression has been linked to increased invasiveness in a number of malignancies, and EZH2 inhibitors are currently being evaluated in clinical trials for cancer therapy . Our findings indicate that inhibiting EZH2 might have therapeutic potential in lupus, suggesting the possibility of pharmacologic repurposing of EZH2 inhibitors as a therapeutic option.…”

Inhibition of EZH2 ameliorates lupus-like disease inMRL/lprmice

“…EZH2 overexpression has been linked to increased invasiveness in a number of malignancies, and EZH2 inhibitors are currently being evaluated in clinical trials for cancer therapy (7). Our data indicate that inhibiting EZH2 might be of therapeutic potential in lupus, suggesting the possibility of pharmacologic repurposing of EHZ2 4 inhibitors as a therapeutic option for lupus.…”

Resveratrol modulates epigenetic regulators of promoter histone methylation and acetylation that restores BRCA1, p53, p21CIP1 in human breast cancer cell lines

“…So far, several KATs (most notably, KAT2A/2B and KAT3A/3B) and 17 KDACs in mammals have been reported . Altered function or overexpression of PRMT5, EZH2, and KDACs is associated with many cancers . Increasing quest for inhibitors of both PRMT5 and EZH2 in recent research as well as clinical trials indicates the immense possibilities of their therapeutic targeting in cancer …”

“…8 Altered function or overexpression of PRMT5, EZH2, and KDACs is associated with many cancers. 6,9,10 Increasing quest for inhibitors of both PRMT5 and EZH2 in recent research as well as clinical trials indicates the immense possibilities of their therapeutic targeting in cancer. 6,[11][12][13] Resveratrol (RVT) a natural polyphenolic compound found in grapes and berries has been widely studied and is considered as an anti-cancer, anti-diabetes, cardioprotective, and antiinflammatory molecule.…”