Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Eur Rev Med Pharmacol Sci. 2020 May;24(9):4775-4784. doi: 10.26355/eurrev_202005_21166.
Previous studies have demonstrated that TNFAIP8 is a cancer-promoting gene. However, the role of TNFAIP8 in esophageal cancer (ECa) has not been reported. The aim of this investigation was to investigate the expression of TNFAIP8 in ECa, and to further explore whether it could regulate cisplatin resistance to this cancer via modulating TAF-Iα expression and promote malignant progression of ECa.
Quantitative Real Time-PCR (qRT-PCR) was performed to examine the expression of TNFAIP8 in 47 tumor tissue specimens and adjacent ones of ECa patients, and the interplay between TNFAIP8 expression and prognosis of patients with ECa was then analyzed. Further, qRT-PCR was applied to verify TNFAIP8 level in ECa cell lines. In addition, the TNFAIP8 knockdown model was constructed in ECa cisplatin-resistant cell lines including EC-109/DDP and OE19/DDP, and then, CCK8 and transwell assays were performed to analyze the impact of TNFAIP8 on the biological function of ECa cells; meanwhile, the Luciferase reporter gene assay and cell reverse experiments were finally conducted to explore its underlying mechanisms.
The qRT-PCR results revealed that the TNFAIP8 level in tumor tissue samples of ECa patients was remarkably higher than that in adjacent ones, and the difference was statistically significant. Similarly, the overall survival rate of patients with high expression of TNFAIP8 was lower when compared with patients with low expression of TNFAIP8. EC-109/DDP and OE19/DDP, the ECa cisplatin-resistant cell lines, were successfully constructed; subsequently, it was found that the proliferation, invasiveness, and metastasis ability of ECa cells in TNFAIP8 knockdown group was remarkably decreased compared with those in the sh-NC group. At the same time, the Western blot results illustrated that the expression of TAF-Iαwas remarkably elevated in the TNFAIP8 knockdown group. In addition, the Luciferase reporting assay and cell reverse experiments also demonstrated that there existed a mutual regulation effect between TNFAIP8 and TAF-Iα, which might together affect the malignant progression of ECa.
The expression of TNFAIP8 was found remarkably enhanced in ECa tissues and cell lines, which might be closely relevant to the poor prognosis of patients with ECa. Additionally, it was found that TNFAIP8 may regulate cisplatin resistance and promote malignant progression of ECa by modulating TAF-Iα expression.
先前的研究表明，TNFAIP8 是一种促进癌症的基因。然而，TNFAIP8 在食管癌（ECa）中的作用尚未被报道。本研究旨在探讨 TNFAIP8 在 ECa 中的表达情况，并进一步研究其是否通过调节 TAF-Iα 的表达来调节顺铂耐药性，从而促进 ECa 的恶性进展。
采用定量实时 PCR（qRT-PCR）检测 47 例食管癌患者肿瘤组织标本及其相邻组织中 TNFAIP8 的表达情况，并分析 TNFAIP8 表达与食管癌患者预后的关系。进一步采用 qRT-PCR 验证 ECa 细胞系中 TNFAIP8 的水平。此外，构建 ECa 顺铂耐药细胞系 EC-109/DDP 和 OE19/DDP 的 TNFAIP8 敲低模型，然后通过 CCK8 和 Transwell 检测分析 TNFAIP8 对 ECa 细胞生物学功能的影响；同时，最后进行荧光素酶报告基因检测和细胞反向实验，探讨其潜在机制。
qRT-PCR 结果显示，食管癌患者肿瘤组织标本中 TNFAIP8 的水平明显高于相邻组织，差异具有统计学意义。同样，高表达 TNFAIP8 的患者总生存率明显低于低表达 TNFAIP8 的患者。成功构建了 ECa 顺铂耐药细胞系 EC-109/DDP 和 OE19/DDP；随后发现，TNFAIP8 敲低组 ECa 细胞的增殖、侵袭和转移能力明显低于 sh-NC 组。同时，Western blot 结果表明，TNFAIP8 敲低组 TAF-Iα 的表达明显升高。此外，荧光素酶报告基因检测和细胞反向实验也表明，TNFAIP8 和 TAF-Iα 之间存在相互调节作用，可能共同影响 ECa 的恶性进展。
TNFAIP8 在食管癌组织和细胞系中的表达明显增强，可能与食管癌患者的不良预后密切相关。此外，发现 TNFAIP8 可能通过调节 TAF-Iα 的表达来调节顺铂耐药性并促进 ECa 的恶性进展。
