Overexpression of EZH2 associated with poor prognosis in gastric cancer promotes
PUBLISHED: 2015-11-27  186 total views, 1 today

Lu Gan

Department of Medical Oncology, Fudan University Shanghai CancerCenter, Shanghai.

ObjectiveDysregulationof EZH2 plays critical oncogenic roles and facilitates tumorigenesis in varioushuman tumor entities. However,theoverall pathophysiological contribution of EZH2 to gastric cancer(GC) remainslargely unknown. Our study aimed to investigate the expression and function ofEZH2 in GC and its possible correlation with clinicopathologicalcharacteristics as well as patient survival. MethodQuantitativereal-time polymerase chain reaction (qRT-PCR) was performed in 170 cases of GC.Pearson analysis was used to calculate the correlation betweenclinicopathological features and the expression of EZH2. Kaplan–Meier curveswith the log rank test and Cox proportional hazards analysis were used toanalyze the overall survival (OS). We also assessed the function and mechanismof EZH2 in vitro by gain-/loss-of-function studies. ResultTheexpression of EZH2 was higher in GC tissues and cells in comparison with theirnormal counterparts. Higher expression of EZH2 led to a significantly poorersurvival and multivariate analysis revealed that EZH2 was an independent riskfactor of OS. Applying loss-of-function and gain-of-function approaches,wedetermined that EZH2 promotes cell growth,andstem cell-like properties. Furthermore,wedemonstrated that enhanced Ezh2 increased levels of the stem cell-like markerOCT-4 and sox2. Conversely,knockdownof EZH2 showed the opposite effect. Finally,weshowed EZH2-overexpress induce AKT phosphorylation,whilesilence EZH2 decreased pAKT. ConclusionOurstudy indicate that the inappropriate activation of EZH2 predicts poorprognosis and have a crucial regulatory role in GC. EZH2 promotes cellproliferation and the acquisition of stem cell-like properties in GC cells viathe AKT signaling pathway. Regulation of the EZH2/AKT pathway may havebeneficial effects on the treatment of GC.

Key Wordsgastriccancer  EZH2

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