EZH2 regulates the malignancy of human glioblastoma cells via modulation of Twist mRNA stability

Glioblastoma multiforme (GBM) is a lethal primary brain tumor with poor survival lifespan and dismal outcome. However, the effects and mechanisms of epigenetic factors on the development of GBM were still not well illustrated. We found that expression of enhancer of zeste homolog 2 (EZH2), which can catalyze histone H3K27me3 to modulate gene expression, was increased in GBM cells. Knockdown of EZH2 can suppress proliferation and migration, while increase temozolomide (TMZ) sensitivity, of GBM cells. Further, knockdown of EZH2 or its specific inhibitor GSK126 can decrease expression of Twist, while over expression of Twist can reverse si-EZH2-suppressed malignancy of GBM cells. Mechanistically, EZH2 can positively regulate mRNA stability of Twist1 mRNA. Further, miR-206, which can bind with 3 ' UTR of Twist1 mRNA, was involved in EZH2regulated mRNA stability of Twist1. Collectively, our data suggest that EZH2 might be a potential target for GBM treatment. Further, miR-206/Twist axis is involved in EZH2-regulated malignancy of GBM cells.

Automated summary

The study revealed that EZH2 expression is increased in glioblastoma multiforme (GBM) cells, and knockdown of EZH2 can suppress cell proliferation and migration while enhancing sensitivity to TMZ. Additionally, EZH2 positively regulates mRNA stability of Twist1, contributing to the malignancy of GBM cells.