TNFAIP8 regulates cisplatin resistance through TAF-Iα and promotes malignant progression of esophageal cancer

D.-L. Zhang, N. Yang

Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China. zdlzdl52973@sina.com

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• Oncology

OBJECTIVE: 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.

PATIENTS AND METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

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