Neoplasma. 2014;61(3):291-8. doi: 10.4149/neo_2014_037.
Zinc finger protein 139(ZNF139), a member of zinc finger protein family, is a transcription factor. Our previous research showed ZNF139 was overexpressed in gastric cancer cells. The purpose of present study is to explore impact and mechanism of ZNF139 on metastasis by regulating invasive ability of gastric cancer cells. Quantitative RT-PCR(QRT-PCR) and Western blot were applied for detection of ZNF139 expression in gastric cancer tissues, adjacent cancer tissues, metastatic lymph nodes, gastric cancer cell lines SGC7901 and BGC823 and gastric epithelial cell line GES-1; siRNA specific to ZNF139 was synthesized and then transfected into gastric cancer cell line BGC823; wound healing assay and Transwell assay were used to observe impact of ZNF139-siRNA after being transfected into BGC823 on its invasion and migration; changes in expression of invasion and migration-related genes MMP-2, MMP-9, ICAM-1 and TIMP1 were detected before and after transfection. Gelatin zymogrphy assay were applied to determine the MMP activities. Statistical analysis was based on the SPSS11.5 software.Expression of ZNF139 in gastric adenocarcinoma tissues and cells was significantly higher than the expression in the adjacent cancer tissues, but lower than the expression in the metastatic lymph nodes; ZNF139 expression was present in gastric cancer cell lines, and the expression level was higher than that in normal gastric epithelial cells lines. ZNF139-siRNA significantly inhibited the invasion and migration activity of gastric cancer cell line BGC823. 48h after ZNF139-siRNA was transfected into gastric cancer cell line BGC823, expression and activity of invasion-related genes MMP-2, MMP-9, ICAM-1 mRNA and protein were significantly inhibited, while expressions of TIMP-1 mRNA and protein were significantly increased. At the same time, the gelatinase activities of MMP2 and MMP9 were decreased by ZNF139 interference.ZNF139 was overexpressed in gastric cancer cells, and the expression was further enhanced in the metastasis process. Knocking down ZNF139 expression in gastric cancer cells could effectively reduce gastric cancer cell invasion and migration ability, and this process might play a role by regulating MMP-TIMP balance.
锌指蛋白 139（ZNF139）是锌指蛋白家族的成员，是一种转录因子。我们之前的研究表明，ZNF139 在胃癌细胞中过表达。本研究旨在通过调节胃癌细胞的侵袭能力来探讨 ZNF139 对转移的影响和机制。实时定量 RT-PCR（QRT-PCR）和 Western blot 用于检测胃癌组织、癌旁组织、转移性淋巴结、胃癌细胞系 SGC7901 和 BGC823 以及胃上皮细胞系 GES-1 中的 ZNF139 表达；合成针对 ZNF139 的 siRNA 并转染入胃癌细胞系 BGC823；通过划痕愈合实验和 Transwell 实验观察转染 BGC823 后 ZNF139-siRNA 对其侵袭和迁移的影响；转染前后检测侵袭和迁移相关基因 MMP-2、MMP-9、ICAM-1 和 TIMP1 的表达变化。明胶酶谱法用于测定 MMP 活性。统计分析基于 SPSS11.5 软件。ZNF139 在胃腺癌组织和细胞中的表达明显高于癌旁组织，但低于转移淋巴结；ZNF139 在胃癌细胞系中表达，表达水平高于正常胃上皮细胞系。ZNF139-siRNA 显著抑制胃癌细胞系 BGC823 的侵袭和迁移活性。转染 BGC823 后 48 小时，侵袭相关基因 MMP-2、MMP-9、ICAM-1mRNA 和蛋白的表达和活性明显受到抑制，而 TIMP-1mRNA 和蛋白的表达明显增加。同时，ZNF139 干扰后 MMP2 和 MMP9 的明胶酶活性降低。ZNF139 在胃癌细胞中过表达，在转移过程中表达进一步增强。敲低胃癌细胞中的 ZNF139 表达可有效降低胃癌细胞的侵袭和迁移能力，这一过程可能通过调节 MMP-TIMP 平衡发挥作用。
