ZNF139 promotes tumor metastasis by increasing migration and invasion in human gastric cancer cells

Abstract

Zinc finger protein 139(ZNF139), a member of zinc finger protein family, is a transcription factor. Our previous research showed ZNF139 was over expressed 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 transected into gastric cancer cell line BGC823; wound healing assay and Trans well assay were used to observe impact of ZNF139-siRNA after being transected 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 transected 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 expressionsofTIMP-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 over expressed 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.