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.
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).
Thus, our findings suggest for the first time that miR-26a promotes invasion/metastasis by inhibiting PTEN and inhibits cell proliferation by repressing EZH2 in HCC.
Increased expression of EZH2 is frequently detected in various cancers including hepatocellular carcinoma (HCC), which is associated with the silencing of tumor suppressor genes.
The epigenetic modificator EZH2 can suppress the expression of immune checkpoint inhibitor PD-L1 by directly upregulating the promoter H3K27me3 levels of CD274 and IRF1 in hepatoma cells, and might serve as a potential therapeutic target for combination of immunotherapy for immune-activated HCC.
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.
The decreased EZH2 markedly increased the expression of a cohort of anti-metastatic genes, including circ-ADD3, by reducing H3K27me3 levels on their promoter regions, which formed a regulatory circuit, thereby dampening HCC metastasis.
Taken together, these findings suggest that LINC00978 promotes HCC progression by inhibiting p21 and E-cadherin expression via EZH2-mediated epigenetic silencing.
Overexpression of EZH2 was critical in repressing TCAM1P-004 and RP11-598D14.1, and EZH2-TCAM1P-004/RP11-598D14.1-regulated pathways were prevalent in human HCC.
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.
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.
The aims of this study were to: validate the use of the immunohistochemical (IHC) markers glutamine synthetase (GS), glypican-3 (GPC3), heat shock protein-70 (HSP70) and enhancer of zeste homologue 2 (EZH2) in liver biopsies for the differential diagnosis between small hepatocellular carcinoma (HCC) and non-neoplastic liver nodules, with special attention to <10-mm nodules; and assess the actual sensitivity and specificity of the single markers, and their combination, in needle biopsies.
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.
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.