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白细胞介素-6通过激活人胶质瘤细胞中的JAK2/STAT3来增加SDCBP表达、细胞增殖和细胞侵袭。

IL-6 increases SDCBP expression, cell proliferation, and cell invasion by activating JAK2/STAT3 in human glioma cells.

作者信息

Cao Fang, Zhang Qiang, Chen Wei, Han Chong, He Yang, Ran Qishan, Yao Shengtao

机构信息

Department of Cerebrovascular Disease, The First Affiliated Hospital of Zunyi Medical CollegeNo. 139, Dalian Avenue, Huichuan District, Zunyi 563000, Guizhou, China.

Department of Stroke Unit and Neurosurgery, The First People's Hospital of ZunyiNo. 98, Fenghuang North Avenue, Huichuan District, Zunyi 563000, Guizhou, China.

出版信息

Am J Transl Res. 2017 Oct 15;9(10):4617-4626. eCollection 2017.

Abstract

Syndecan-binding protein (SDCBP), which is induced by tumor necrosis factor-α and interferon-γ, controls the proliferation and invasion of several different types of cancer cells. Interleukin-6 (IL-6) is known to play an important role in the glioma cell growth and invasion. The present study aimed to investigate the relationship between IL-6 and SDCBP in glioma cells. SDCBP expression was knocked down in two glioma cell lines (T98G and U87) by small interfering RNA (siRNA) transfection. Cell proliferation and invasion were significantly repressed following SDCBP knockdown, and there was a positive correlation between SDCBP and IL-6 expression levels in glioma tissues. IL-6 stimulation dose- and time-dependently induced SDCBP expression at both mRNA and protein levels. Furthermore, pre-treatment with the Janus kinase 2 (JAK2) inhibitor AG490 abolished the IL-6-induced SDCBP expression, suggesting that the effect of IL-6 on SDCBP transcription is dependent on JAK2/signal transducer and activator of transcription 3 (STAT3) signaling. Finally, IL-6 did not stimulate glioma cell growth or invasion when SDCBP expression was suppressed. In summary, our results suggest that IL-6 promotes glioma cell proliferation and invasion by inducing SDCBP expression, which is mediated by JAK2/STAT3 signaling.

摘要

硫酸乙酰肝素蛋白聚糖结合蛋白(SDCBP)由肿瘤坏死因子-α和干扰素-γ诱导产生,可控制多种不同类型癌细胞的增殖和侵袭。白细胞介素-6(IL-6)在胶质瘤细胞的生长和侵袭中发挥重要作用。本研究旨在探讨胶质瘤细胞中IL-6与SDCBP之间的关系。通过小干扰RNA(siRNA)转染,在两种胶质瘤细胞系(T98G和U87)中敲低SDCBP表达。敲低SDCBP后,细胞增殖和侵袭受到显著抑制,且胶质瘤组织中SDCBP与IL-6表达水平呈正相关。IL-6刺激在mRNA和蛋白质水平上均呈剂量和时间依赖性地诱导SDCBP表达。此外,用Janus激酶2(JAK2)抑制剂AG490预处理可消除IL-6诱导的SDCBP表达,提示IL-6对SDCBP转录的影响依赖于JAK2/信号转导及转录激活因子3(STAT3)信号通路。最后,当SDCBP表达受到抑制时,IL-6不会刺激胶质瘤细胞生长或侵袭。总之,我们的结果表明,IL-6通过诱导SDCBP表达促进胶质瘤细胞增殖和侵袭,这一过程由JAK2/STAT3信号通路介导。

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