Enhancer of zeste homolog 2 (EZH2), the critical component of polycomb group protein family, has been demonstrated to be overexpressed in various types of human cancer, including hepatocellular carcinoma, breast, bladder and lung cancer.
Enhancer of zeste homolog 2 (EZH2), an oncogene responsible for the tri-methylation of histone H3 at lysine 27 (H3K27me3), was identified to be overexpressed in approximate 70-90% of HCC cases, which prompted us to investigate whether or how AR regulates EZH2 expression.
EZH2 was a direct downstream target gene of miR-137 in HCC and miR-137 suppressed invasion and migration by targeting EZH2-STAT3 signaling in HCC cells.
A significant association between FHL1 and EZH2 expression was identified in the female hepatocellular carcinoma (HCC) samples, but was not in the male HCC samples.
Accordingly, the expression of lnc-β-Catm, EZH2 and Wnt-β-catenin targets is positively correlated with cancer severity and prognosis of people with HCC.
Among these dysregulated RNAs, three DELs (AP002478.1, HTR2A-AS1, and ERVMER61-1) and six DEGs (enhancer of zeste homolog 2 [<i>EZH2</i>], kinesin family member 23 [<i>KIF23</i>], chromobox 2 [<i>CBX2</i>], centrosomal protein 55 [<i>CEP55</i>], cell division cycle 25A [<i>CDC25A</i>], and claspin [<i>CLSPN</i>]) were used for construct a prognostic signature for HCC overall survival (OS), and performed well in HCC OS (adjusted <i>P</i><0.0001, adjusted hazard ratio = 2.761, 95% confidence interval = 1.838-4.147).
By interrogating the miRNA expression profile in EZH2-knockdown cell lines and primary HCC samples, we identified a subset of miRNA that was epigenetically suppressed by EZH2 in human HCC.
c-Myc collaborates with EZH2-containing PRC2 complex in silencing tumor-suppressive miRNAs during hepatocarcinogenesis and provides promising therapeutic candidates for human HCC.
Cancer-associated fibroblasts promote angiogenesis of hepatocellular carcinoma by vascular endothelial growth factor-mediated enhancer of zeste homolog-2/vasohibin 1 pathway and may be a potentially useful therapeutic target for hepatocellular carcinoma.
Collectively, these results demonstrate that EZH2 inhibition enhances HCC eradication by NK cells and that EZH2 functions, in part, as an oncogene by inhibiting immune response.
Collectively, we proposed a novel model for an EZH2 - miRNAs - IGF1R regulatory axis, which might provide insights into how EZH2 contributes to sorafenib resistance in HCC.
Gene expression analysis of human HBV-associated HCC specimens demonstrated concordant overexpression of YY1 and EZH2, which correlated with poor survival of patients in advanced stages.