EZH2 promotes tumor progression by increasing VEGF expression in clear cell renal cell carcinoma

ABSTRACT

Objectives. The present study is to evaluate the expression level of enhancer of zeste homolog 2 (EZH2) and vascular endothelial growth factor (VEGF), and analyze their correlations with clinicopathological characteristics and survival in patients with clear cell renal cell carcinoma (CCRCC). The effect of EZH2 on apoptosis and cell proliferation in 786-O renal cancer cell line is investigated. Methods. The expression level of EZH2 and VEGF was detected in 185 primary CCRCC patients’ tissues using tissue microarray and immunohistochemistry. Small interfering RNA or enhanced green fluorescent protein transfection was employed to investigate the effect of EZH2 inhibition or overexpression on VEGF expression, apoptosis and cell proliferation in 786-O cells using flow cytometry, immunofluorescence microscopy, quantitative real-time reverse-transcription polymerase chain reaction and Western blot analysis. Results. High expression level of EZH2 and VEGF was observed in advanced CCRCC and correlated with the TNM stage (p = 0.013, p = 0.001) and distant metastasis (p = 0.011, p = 0.038), respectively. EZH2 was positively correlated with VEGF in CCRCC tissues (correlation coefficient = 0.850, p < 0.001). Kaplan–Meier survival analysis revealed that patients with positive EZH2 expression had a shorter overall survival time compared to patients with negative EZH2 expression (34.3 vs. 67.2, p < 0.001). In 786-O cells, EZH2 silencing inhibited VEGF expression and cell proliferation while increasing apoptosis (p < 0.001). EZH2 overexpression promoted VEGF expression and cell proliferation while inhibiting apoptosis (p < 0.001). Conclusions. EZH2 correlates positively with VEGF and associates with adverse clinicopathologic characteristics and shorter survival time in CCRCC patients. EZH2 accelerates antiapoptosis and cell cycle in 786-O cells (AU)

RESUMEN

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