Department of Gastroenterology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Eur Rev Med Pharmacol Sci. 2020 Apr;24(8):4246-4254. doi: 10.26355/eurrev_202004_21004.
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.
先前的研究发现 IPO5 是一种促进癌症的基因。然而，IPO5 在食管癌中的作用尚未被报道。本研究旨在探讨 IPO5 在食管癌中的表达特征，并进一步分析其与食管癌临床参数和预后的关系。
采用实时定量聚合酶链反应（qRT-PCR）检测 45 对食管癌患者肿瘤组织标本及其相邻正常组织中基质金属蛋白酶 7（MMP7）的表达。分析 IPO5 表达与食管癌患者临床指标和预后的相关性。同时，采用 qRT-PCR 检测食管癌细胞系中 IPO5 的表达。此外，通过细胞计数试剂盒-8（CCK-8）和 5-乙炔基-2'-脱氧尿苷（EdU）检测分析 IPO5 对食管癌细胞功能的影响。最后，通过双荧光素酶报告基因检测和细胞反向实验探讨其潜在机制。
本实验中，qRT-PCR 结果表明食管癌患者肿瘤组织中 IPO5 的表达明显高于相邻正常组织，差异具有统计学意义。与 IPO5 低表达的食管癌患者相比，IPO5 高表达的患者病理分期更高，总生存率更低。与对照组相比，IPO5 敲低组的食管癌细胞增殖能力明显降低。此外，Western blot 结果表明，在 IPO5 敲低的食管癌细胞系中，关键蛋白 MMP7 的表达显著升高。双荧光素酶报告基因检测结果表明，IPO5 可特异性结合 MMP7。此外，细胞反向实验表明，MMP7 是 IPO5 调节的食管癌恶性进展的关键蛋白。
IPO5 在食管癌组织中表达显著增加，与食管癌患者的病理分期和预后不良相关。IPO5 可能通过调节 MMP7 促进食管癌的恶性进展。
