Abstract
Although enhancer of zeste homolog 2 (EZH2) has been reported as an independent prognostic factor in renal cell carcinoma (RCC), little is known about the exact mechanism of EZH2 in promoting the genesis of RCC. However, several studies have shown that dysregulation of the Wnt/β-catenin signaling pathway plays a crucial role. Therefore, we determined whether EZH2 could affect ACHN human RCC cell proliferation and invasion via the Wnt/β-catenin pathway. In the present study, we investigated the effects of short interfering RNA (siRNA)-mediated EZH2 gene silencing on Wnt/β-catenin signaling in ACHN cells. EZH2-siRNA markedly inhibited the proliferation and invasion capabilities of ACHN, while also reducing the expression of EZH2, Wnt3a and β-catenin. In contrast, cellular expression of GSK-3β (glycogen synthase kinase-3β), an inhibitor of the Wnt/β-catenin pathway, was conspicuously higher after transfection of EZH2 siRNA. These preliminary findings suggest EZH2 may promote proliferation and invasion of ACHN cells via action on the Wnt/β-catenin signaling pathway.
Highlights
The enhancer of zeste homolog 2 (EZH2), as a homolog of the Drosophila Enhancer of zeste (E (z)), is the catalytic subunit of the Polycomb-Repressive Complex 2/3 (PRC2/3), which has been found to contribute to the initiation of gene repression through lysine 27 of histone H3 (H3K27) trimethylation (Ciarapica et al, 2011)
Wagener et al (2008) reported that EZH2 was overexpessed in many renal cell carcinoma (RCC) cell lines, including the ACHN cell
They further demonstrated that short interfering RNA (siRNA)-mediated inhibition of EZH2 expression could conspicuously decrease the growth rate and increase apoptosis in RCC cell lines of 786-O and CaKi-1
Summary
The enhancer of zeste homolog 2 (EZH2), as a homolog of the Drosophila Enhancer of zeste (E (z)), is the catalytic subunit of the Polycomb-Repressive Complex 2/3 (PRC2/3), which has been found to contribute to the initiation of gene repression through lysine 27 of histone H3 (H3K27) trimethylation (Ciarapica et al, 2011). EZH2 has been reported to be involved in several key regulatory mechanisms in human cells, such as embryogenesis, lymphocytes and central nervous systems development (Montgomery et al, 2007; Sher et al, 2008; Thiel et al, 2011). Wagener et al (2010) documented that EZH2 could be considered an independent prognostic factor in renal cell carcinoma (RCC). They advanced pointed out that EZH2 knockdown mediated by RNA interference (RNAi) in several RCC cell lines could reduce tumor cell proliferation and increase apoptosis (Wagener et al, 2008). There are few articles referring to the internal mechanism of EZH2 in promoting oncogenesis of RCC
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