Inhibition of enhancer of zeste homolog 2 and human mutL homolog 1 suppresses progression of glioma
Objective To investigate the role of enhancer of zeste homolog 2(EZH2)and human mutL homolog 1(hMLH1)in glioma.Methods The small interfering RNA(siRNA)targeting EZH2 and hMLH1 was designed and synthesized,and transfected into U-87 cells.The control group and knockdown group were set up,and the proliferation of the two groups was analyzed through 5-Ethynyl-2'-deoxyuridine(EdU)proliferation assay.T test was used for comparison between groups.Results The results showed that the mRNA levels of EZH2(7.97±0.14,6.00±0.18,6.24±0.11,t=83.80,47.18,83.55)and hMLH1(6.15±0.08,3.93±0.17,4.25±0.12,t=103.700,29.800,45.510)were significantly higher in glioma tissues and cells than their normal counterparts(P＜0.01).Transfection of siRNA into U-87 glioma cells resulted in decreased cell proliferation capacity,with the control group being(68.2± 14.8),EZH2 knockdown group being(33.5±13.1),and hMLH1 knockdown group being(43.1± 10.0).After knocking down EZH2 and hMLH1 expression,cell apoptosis of transfected cells was en-hanced(t=3.041,2.934,P＜0.05).The ratio of p-MEK1/MEK1 and p-ERK1/ERK1 was down-regula-ted after silencing the level of p-MEK(t=5.590,6.548,P＜0.05)and p-ERK1(t=10.730,9.260,P＜0.05).The inhibitory effects were enhanced(t=6.425,7.273,P＜0.05)in U-87 cells that were co-transfected with EZH2-siRNA and hMLH1-siRNA as compared with those that were transfected individual-ly.Conclusion The findings show that the inhibition of EZH2 and hMLH1 impacts glioma growth and cell death likely via in-activating the MEK/ERK pathway.
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