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EBV Rta 诱导的 IL-6 通过 IL-6R/JAK/STAT3 通路促进旁观者肿瘤细胞迁移。

EBV Rta-induced IL-6 Promotes Migration of Bystander Tumor Cells Through IL-6R/JAK/STAT3 Pathway .

机构信息

Department of Dental Technology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan, R.O.C.

Department of Pathology, Golden Hospital, Pingtung, Taiwan, R.O.C.

出版信息

Anticancer Res. 2020 Jun;40(6):3255-3264. doi: 10.21873/anticanres.14307.

Abstract

BACKGROUND/AIM: Rta, a transactivator of Epstein-Barr virus, is associated with progression of nasopharyngel carcinoma (NPC); however, its mechanism of contribution to the pathogenesis of NPC remains unclear. Interleukin-6 (IL-6), a tumor promoter, is detected in NPC. This in vitro study examined whether and how Rta promotes NPC progression by up-regulating IL-6.

MATERIALS AND METHODS

Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), quantitative real-time PCR, ELISA, immunoblotting assays, reporter gene assays, and transwell migration assays were performed.

RESULTS

In NPC cells, Rta up-regulated IL-6 expression at the mRNA and protein levels, and the Rta's C-terminus was essential for promoter activation and expression of IL-6. The induction of IL-6 by Rta also required activation of extracellular signal-regulated kinase 1/2 and activator protein-1. Furthermore, IL-6 secreted from Rta-expressing NPC cells promoted migration of Rta-negative NPC cells by activating IL-6 receptor/Janus kinase/signal transducer and activator of transcription 3 pathway.

CONCLUSION

Rta contributes to progression of NPC cells through induction of IL-6 in vitro.

摘要

背景/目的: Epstein-Barr 病毒的反式激活因子 Rta 与鼻咽癌(NPC)的进展相关;然而,其促进 NPC 发病机制的机制尚不清楚。白细胞介素-6(IL-6)是一种肿瘤促进剂,在 NPC 中检测到。这项体外研究检测了 Rta 是否以及如何通过上调 IL-6 促进 NPC 的进展。

材料和方法

半定量逆转录-聚合酶链反应(RT-PCR)、定量实时 PCR、ELISA、免疫印迹分析、报告基因分析和 Transwell 迁移分析。

结果

在 NPC 细胞中,Rta 在 mRNA 和蛋白水平上上调了 IL-6 的表达,Rta 的 C 端对于启动子激活和 IL-6 的表达至关重要。Rta 诱导的 IL-6 也需要细胞外信号调节激酶 1/2 和激活蛋白-1 的激活。此外,Rta 表达的 NPC 细胞分泌的 IL-6 通过激活 IL-6 受体/Janus 激酶/信号转导和转录激活因子 3 通路促进 Rta 阴性 NPC 细胞的迁移。

结论

Rta 通过体外诱导 IL-6 促进 NPC 细胞的进展。

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