Inhibitors of enhancer of zeste homolog 2 (EZH2) activate tumor-suppressor microRNAs in human cancer cells.
作者： S Hibino , Y Saito , T Muramatsu , A Otani , Y Kasai
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摘要: Enhancer of zeste homolog 2 (EZH2) enhances tumorigenesis and is commonly overexpressed in several types cancer. To investigate the anticancer effects EZH2 inhibitors, microRNA (miRNA) expression profiles were examined gastric liver cancer cells treated with suberoylanilide hydroxamic acid (SAHA) 3-deazaneplanocin A (DZNep). We confirmed that SAHA DZNep suppressed AGS HepG2 inhibited their proliferation. The results microarray analyses demonstrated miR-1246 was upregulated by treatment DZNep. MiR-302a miR-4448 markedly DZNep, respectively. DYRK1A, CDK2, BMI-1 Girdin, which are targets miR-1246, miR-302a miR-4448, leading to apoptosis, cell cycle arrest reduced migration cells. ChIP assay revealed binding promoter regions miR-4448. These findings suggest inhibitors such as exert multiple through activation tumor-suppressor miRNAs.
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