Down-regulation of EZH2 by RNA Interference Inhibits Proliferation and Invasion of ACHN Cells via the Wnt/β-catenin Pathway

Yuan, Jun-Bin; Liu, Yang; Zu, Xiongbing; Qi, Lin

doi:10.7314/apjcp.2012.13.12.6197

Cited by 9 publications

(9 citation statements)

References 28 publications

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“…EZH2 is the histone H3 lysine 27 methyltransferase of polycomb-repressive complex 2 and is overexpressed in multiple cancer types (62). Several EZH2-related proteins were detected by western blot analysis in both A549 and non-small cell lung cancer (NSCLC) H1299 cell lines and decreased expression of both β-catenin and bcl-2 was found in consensus with the previous finding that EZH2 can ultimately enhance Bcl-2 expression via the activation of wnt/β-catenin signaling (63). Thus, Huaier may induce apoptosis in lung cancer cells via the miR-26b-5p-EZH2-mediated wnt/β-catenin pathway (Fig.…”

Section: Apoptosis Induction By Huaiersupporting

confidence: 73%

The anticancer effect of Huaier (Review)

Song

Zhang

2015

Oncology Reports

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Abstract. Trametes robiniophila Murr. (Huaier) is a sandy beige mushroom found on the trunks of trees and has been widely used in traditional Chinese medicine (TCM) for ~1,600 years. The anticancer effects of Huaier have attracted increasing worldwide interest in recent years. Accumulating evidence suggests that the anticancer mechanism of Huaier may be associated with various biological activities, such as inhibition of cell proliferation, anti-metastasis, interference with tumor angiogenesis and tumor-specific immunomodulatory effect. Animal and experimental studies suggest that Huaier is a promising anticancer agent. Further clinical research is warranted to illustrate the untapped chemopreventive and therapeutic potential of Huaier either alone or in conjunction with existing therapies.

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Section: Apoptosis Induction By Huaiersupporting

confidence: 73%

The anticancer effect of Huaier (Review)

Song

Zhang

2015

Oncology Reports

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“…Here, we confirmed that the Wnt/β-catenin pathway was stimulated by EZH2 in HeLa and SiHa cells, with activation of target genes, resulting in the promotion of cell growth and tumor formation (Figure 4). Additionally, EZH2-stimulated epigenetic silencing contributes to constitutive activation of Wnt/β-catenin signaling and consequential cellular proliferation in hepatocellular carcinoma [55], gastric cancer [28], renal cell carcinoma [56], colon cancer [57] and breast cancer [58]. In the mechanism of the EZH2-mediated activation of Wnt/β-catenin signaling to promote carcinogenesis, EZH2, which acts as a transcriptional repressor, represses Wnt antagonists, including RAF1, CXXC4, AXIN2/betaTrCP and p53 [13, 28, 55, 59], by decreasing the acetylation of H3K27, thereby promoting the development of different types of cancers.…”

Section: Discussionmentioning

confidence: 99%

“…In a previous study, GSK-3β expression was found to be markedly increased after transfection of EZH2 siRNA to promote the proliferation and invasion of ACHN cells via activation of the Wnt/β-catenin signaling pathway [56]. TP53 was first verified as a target gene of EZH2 in cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

EZH2-mediated repression of GSK-3β and TP53 promotes Wnt/β-catenin signaling-dependent cell expansion in cervical carcinoma

2016

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Enhancer of zeste homolog 2 (EZH2), a catalytic core component of the Polycomb repressive complex 2 (PRC2), stimulates the silencing of target genes through histone H3 lysine 27 trimethylation (H3K27me3). Recent findings have indicated EZH2 is involved in the development and progression of various human cancers. However, the exact mechanism of EZH2 in the promotion of cervical cancer is largely unknown. Here, we show that EZH2 expression gradually increases during the progression of cervical cancer. We identified a significant positive correlation between EZH2 expression and cell proliferation in vitro and tumor formation in vivo by the up-regulation or down-regulation of EZH2 using CRISPR-Cas9-mediated gene editing technology and shRNA in HeLa and SiHa cells. Further investigation indicated that EZH2 protein significantly accelerated the cell cycle transition from the G0/G1 to S phase. TOP/FOP-Flash reporter assay revealed that EZH2 significantly activated Wnt/β-catenin signaling and the target genes of Wnt/β-catenin pathway were up-regulated, including β-catenin, cyclin D1, and c-myc. Moreover, dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays confirmed that EZH2 inhibited the expression of glycogen synthase kinase-3β (GSK-3β) and TP53 through physically interacting with motifs in the promoters of the GSK-3β and TP53 genes. Additionally, blockage of the Wnt/β-catenin pathway resulted in significant inhibition of cell proliferation, and activation of the Wnt/β-catenin pathway resulted in significant enhancement of cell proliferation, as induced by EZH2. Taken together, our data demonstrate that EZH2 promotes cell proliferation and tumor formation in cervical cancer through activating the Wnt/β-catenin pathway by epigenetic silencing via GSK-3β and TP53.

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“…Evidently, the Wnt/β-catenin signaling pathway serves a crucial role in cell proliferation and tumor cell invasion (40)(41)(42). The effect on the expression of the Wnt/β-catenin signaling pathway was investigated in the present study by western blotting in order to elucidate the underlying mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Astrocyte elevated gene-1 promotes the proliferation and invasion of breast cancer cells by activating the Wnt/β-catenin signaling pathway

Dai

Wang

et al. 2017

Oncology Letters

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Abstract. Astrocyte elevated gene-1 (AEG1) was identified to be overexpressed in breast cancer, and to be associated with the development of breast cancer. In the present study, AEG1 was identified as highly expressed in the MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cell lines and was detected in the MCF-10A normal breast epithelial cell line. The present study established an AEG1-knockdown MCF-7 cell line to investigate the expression status of certain cancer-associated proteins. Western blotting demonstrated that AEG1 may affect cancer cell proliferation and invasion via activating the Wnt/β-catenin signaling pathway, a hypothesis that has been supported by cell function tests. The results of the present study demonstrated that when AEG1 was significantly overexpressed in breast cancer cells it promoted cell proliferation and invasion via activating the Wnt/β-catenin signaling pathway. Therefore, AEG1 may serve as a novel therapeutic target in breast cancer. IntroductionBreast cancer is a common type of malignancy; the incidence of the disease has increased in recent years worldwide, currently ranking first with respect to cancer-associated morbidity in women (1-3). The traditional methods of treatment include surgery, radiotherapy and chemotherapy for patients with advanced breast cancer exhibit poor efficacy (4). Therefore, the development of gene-targeted therapy for breast cancer requires further attention. Previous studies have revealed that numerous genes are involved in the occurrence and development of breast cancer, including cyclin D1, matrix metalloproteinases (MMPs) and E-cadherin (5-8). Astrocyte elevated gene-1 (AEG1) has also been investigated with respect to poor prognosis in breast cancer (9). AEG1 is a potentially crucial mediator of tumor malignancy and a key converging point of a complex network of oncogenic signaling pathways (10-12). Previous studies revealed that the AEG1 gene was significantly overexpressed in a number of types of malignant cells, and is associated with tumorigenesis, proliferation, invasion and metastasis (13,14). Statistics also demonstrated that AEG1 was upregulated in breast cancer tissue and positively correlated with clinical stage and lymph node metastasis (15).The Wnt signaling pathway is one of the most important intracellular signal transduction pathways, and it affects the activated state of multiple effector molecules downstream (16)(17)(18)(19). It is closely associated with a variety of human tumor developments, and serves an important role in breast cancer cell proliferation and invasion (20,21). However, the mechanisms that underlie the activation of the Wnt signaling pathway in various types of breast cancer have yet to be identified. β-catenin has been revealed as a central regulator in the Wnt signaling pathway, and is associated with disease progression and poor prognosis in breast cancer (22). Typically, during activation of the Wnt signaling pathway, β-catenin accumulates in the cytosol at high levels, binds to T-cell factor/lymphoid enhancer fac...

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Down-regulation of EZH2 by RNA Interference Inhibits Proliferation and Invasion of ACHN Cells via the Wnt/β-catenin Pathway

Cited by 9 publications

References 28 publications

The anticancer effect of Huaier (Review)

The anticancer effect of Huaier (Review)

EZH2-mediated repression of GSK-3β and TP53 promotes Wnt/β-catenin signaling-dependent cell expansion in cervical carcinoma

Astrocyte elevated gene-1 promotes the proliferation and invasion of breast cancer cells by activating the Wnt/β-catenin signaling pathway

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