IPO5 promotes malignant progression of esophageal cancer through activating MMP7.

Abstract

Previous studies have found that IPO5 is a cancer-promoting gene. However, the role of IPO5 in esophageal cancer has not been reported. This study aims to investigate the expression characteristics of IPO5 in esophageal cancer, and to further analyze its relationship with clinical parameters and prognosis of esophageal cancer. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression of matrix metalloproteinase 7 (MMP7) in 45 pairs of tumor tissue specimens and adjacent normal ones collected from esophageal cancer patients. The correlation between IPO5 expression and clinical indicators and prognosis of esophageal cancer patients was analyzed. Meanwhile, IPO5 expression in esophageal cancer cell lines was also detected using qRT-PCR. In addition, the influence of IPO5 on esophageal cancer cell functions was analyzed using cell counting kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) assays. Finally, Dual-Luciferase reporter assay and cell reverse experiments were conducted to explore its underlying mechanisms. In this experiment, qRT-PCR results indicated that IPO5 expression in tumor tissues of esophageal cancer patients was significantly higher than that in adjacent normal ones, and the difference was statistically significant. Compared with esophageal cancer patients with low expression of IPO5, those with high expression of IPO5 had higher pathological stage and lower overall survival rate. Compared with control group, the proliferation ability of esophageal cancer cells in IPO5 knockdown group was significantly decreased. In addition, Western Blot results indicated that the key protein MMP7 was conspicuously elevated in the esophageal cancer cell line after knockdown of IPO5. Dual-Luciferase reporter assay results suggested that IPO5 can specifically bind MMP7. Additionally, the cell reverse experiment demonstrated that MMP7 was responsible for IPO5-regulated malignant progression of esophageal cancer. IPO5 expression significantly increased in esophageal cancer tissues, which was associated with pathological staging and poor prognosis of esophageal cancer patients. IPO5 may promote malignant progression of esophageal cancer through the regulation of MMP7.