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.
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.
These results, collectively, uncover that CLDN14 is a novel direct target of EZH2-mediated H3K27ME3, and provide an explanation for the aggressive nature of HCC with downregulation of CLDN14 and the underling mechanism that links the tumor suppressor CLDN14 to the wnt/β-catenin signaling pathway.
Our results showed that the SNHG20/EZH2/E-cadhein regulator pathway might contribute to the development of novel therapeutic strategies for HCC patients.
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.
The expression of Bmi1 and EZH2 was heterogeneous and associated with vascular infiltration, the histological grades, and the cell proliferation activity in HCC and HC-CC.
The coexistence of 14-3-3σ and EZH2 overexpression is associated with a relatively unfavorable prognosis (p<0.01), suggesting that aberrant upregulation of 14-3-3σ and EZH2 expression serves as an inferior prognostic biomarker for HCC.
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.
These findings uncovered, for the first time, a mutual suppression regulation between CHD5 and EZH2, which may provide new insights into their potential therapeutic significance for 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.
Overexpression of HOXD-AS1 competitively bound to miR-130a-3p that prevented SOX4 from miRNA-mediated degradation, thus activated the expression of EZH2 and MMP2 and facilitated HCC metastasis.
Taken together, these findings suggest that LINC00978 promotes HCC progression by inhibiting p21 and E-cadherin expression via EZH2-mediated epigenetic silencing.
These findings show that elevated EZH2 contributes to miR-101 deregulation in HCC and highlight the coordinated role of miR-101 and EZH2 in hepatocarcinogenesis.
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.