目的：通过转染Zeste同源物增强子2（enhancer of zeste homolog 2，EZH2）过表达或者敲低载体，探讨EZH2和Lys27位点三甲基化组蛋白H3（histone H3 methylated Lys27，H3K27me3）对食管麟状细胞癌（esophageal squamous cell cancer，ESCC）细胞迁移和侵袭能力的影响。方法：应用实时荧光定量PCR、Western blotting法检测ESCC细胞株KYSE30、KYSE170、TE1、Eca109中EZH2 mRNA水平,以及ESCC细胞过表达或者敲低EZH2对H3K27me3表达水平的影响。用划痕实验及Transwell侵袭实验分析过表达或者敲低EZH2后ESCC细胞的迁移侵袭能力。用实时荧光定量PCR法分析ESCC细胞过表达及敲低EZH2对MMPs mRNA水平的影响。结果：食管癌Eca109及TE1细胞中EZH2和H3K27me3 mRNA和蛋白水平明显高于KYSE30及KYSE170细胞（P<0.05）。过表达EZH2的食管癌KYSE30及KYSE170 细胞H3K27me3蛋白的表达水平显著升高（P<005），敲低EZH2后Eca109及TE1细胞H3K27me3蛋白的表达水平明显降低（P<0.05）。过表达EZH2后，KYSE30及KYSE170细胞的穿膜数目明显增多\[（281.33±4.10）、（241.67±4.04） vs （132.00±4.00）、（105.33±3.51）个，均P<005\]、迁移距离明显增大\[（63.6±1.2）、（62.5±2.5） vs （23.0±2.3)、（21.2±1.0）μm，P<0.05\]。敲低EZH2后Eca109及TE1细胞的穿膜数目显著减少（均P<0.05），转染shEZH2后Eca109 及 TE1细胞迁移的距离明显减小（均P<005）。结论：EZH2可增加靶基因启动子上组蛋白H3第27位赖氨酸的三甲基化，并增强ESCC细胞的迁移和侵袭能力。

Objective:To study the effect of enhancer of zeste homolog 2(EZH2) and histone H3 methylated Lys27 (H3K27me3) on the migration and invasion ability of esophageal squamous cell cancer (ESCC) cells by transfection of vectors expressing/knock down EZH2. Methods: Quantificational real-time PCR(qRT-PCR) and Western blotting were performed to evaluate the expression levels of EZH2in esophageal carcinoma cell lines (KYSE30, KYSE170, TE1, Eca109), as well as the effect of over-expression or knockdown of EZH2 on H3K27me3 expression in ESCC cell lines. Effect of EZH2 over-expression or knockdown on migration and invasion abilities of ESCC cells were examined by wound healing assay and Transwell invasion test, respectively. The expression level of MMPs in ESCC cells after over-expression or knockdown of EZH2 were detected by qRT-PCR.Results: The expressions of EZH2 and H3K27me3 in Eca109 and TE1 cells were significantly higher than those in KYSE30 and KYSE170 cells (P<0.05). Over-expression of EZH2 promoted the expression of H3K27me3 in KYSE30 and KYSE170 cell lines (P<0.05). Knockdown of EZH2inhibited the expression of H3K27me3 in Eca109 and TE1 cell lines (P<0.05). The trans-membrane number of KYSE30 and KYSE170 cells was significantly increased (\[281.33±4.10\] vs \[132.00±4.00\], P<0.05; \[241.67±4.04\] vs \[105.33±3.51\], P<0.05), and the migration distance of KYSE30 and KYSE170 cells was significantly increased (\[63.6±1.2\] vs \[23.0±2.3\] μm, P<0.05; \[62.5±2.5\] vs \[21.2±1.0\] μm, P<0.05) after over-expression of EZH2. Knockdown of EZH2significantly decreased the trans-membrane number of Eca109 and TE1 cells (all P<0.05), and the migration distance was also decreased after transfection with shEZH2 (all P<0.05). Conclusion: EZH2 can enhance trimethylation of lysine 27 on histone H3 (H3K27) of the target gene promoters, and promote the migration and invasion abilities of esophageal carcinoma cell lines.

河北省科技支撑计划资助项目（No.14277732D，No.152777184)