Institute of Cardiothoracic Surgery, Changhai Hospital, 168, Changhai Rd, Shanghai, PR China.
Mol Cancer. 2012 Aug 6;11:51. doi: 10.1186/1476-4598-11-51.
The enhancer of zeste homolog 2 (EZH2) was found to be overexpressed and associated with tumor metastasis in esophageal squamous cell carcinoma (ESCC). On the other hand, it was reported that miR-26a, miR-98, miR-101, miR-124, miR-138 and miR-214 could inhibit the expression of EZH2 in some tumors. However, the role of miRNAs in the regulation of EZH2 expression in human ESCC has not been documented. The aim of this study was to determine the role of these miRNAs in the regulation of tumor metastasis via EZH2 overexpression in human ESCC.
The expression of these miRNAs and EZH2 mRNA were examined by qPCR and the expression of EZH2 protein was detected by western blot. The role of these miRNAs in migration and invasion was studied in ESCC cell line (Eca109) transfected with miRNA mimics or cotransfected with miRNA mimics and pcDNA-EZH2 plasmid (without the 3'-UTR of EZH2). Through clinical investigation, we found that miR-98 and miR-214 expression was significantly lower in ESCC tissues than in matched normal tissues, and the expression level of miR-98 and miR-214 was inversely correlated to EZH2 protein expression and the clinical features such as pathological grade, tumor stage and lymph node metastasis in ESCC. In Eca109 cells, overexpression of miR-98 and miR-214 significantly inhibited the migration and invasion of ESCC cells, which was reversed by transfection of EZH2.
These findings suggest that decreased expression of miR-98 and miR-214 might promote metastasis of human ESCC by inducing accumulation of EZH2 protein.
在食管鳞状细胞癌（ESCC）中，发现增强子的锌指蛋白 2（EZH2）过表达并与肿瘤转移相关。另一方面，据报道 miR-26a、miR-98、miR-101、miR-124、miR-138 和 miR-214 可以在某些肿瘤中抑制 EZH2 的表达。然而，miRNAs 在调节人 ESCC 中 EZH2 表达中的作用尚未有文献记载。本研究旨在确定这些 miRNA 通过 EZH2 过表达在人 ESCC 中对肿瘤转移的调节作用。
通过 qPCR 检测这些 miRNA 和 EZH2 mRNA 的表达，通过 Western blot 检测 EZH2 蛋白的表达。通过转染 miRNA 模拟物或共转染 miRNA 模拟物和 pcDNA-EZH2 质粒（无 EZH2 的 3'-UTR）的 ESCC 细胞系（Eca109）研究这些 miRNA 在迁移和侵袭中的作用。通过临床研究，我们发现 miR-98 和 miR-214 在 ESCC 组织中的表达明显低于匹配的正常组织，miR-98 和 miR-214 的表达水平与 EZH2 蛋白表达以及 ESCC 的临床特征如病理分级、肿瘤分期和淋巴结转移呈负相关。在 Eca109 细胞中，miR-98 和 miR-214 的过表达显著抑制了 ESCC 细胞的迁移和侵袭，而 EZH2 的转染则逆转了这一现象。
这些发现表明，miR-98 和 miR-214 的表达降低可能通过诱导 EZH2 蛋白的积累促进人 ESCC 的转移。
