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CUEDC2 通过抑制 STAT3 和 NF-κB 信号通路的激活来抑制神经胶质瘤的致瘤性。

CUEDC2 suppresses glioma tumorigenicity by inhibiting the activation of STAT3 and NF-κB signaling pathway.

机构信息

Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China.

School of Nursing, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China.

出版信息

Int J Oncol. 2017 Jul;51(1):115-127. doi: 10.3892/ijo.2017.4009. Epub 2017 May 17.

Abstract

CUEDC2, a CUE domain containing 2 protein, plays critical roles in many biological processes, such as cell cycle, inflammation and tumorigenesis. However, whether CUEDC2 was involved in tumorigenesis of glioma and the possible mechanism remains to be elucidated. In the present study, our results implied that the expression of CUEDC2 was lower in the glioma tissue and glioma cell lines than that of normal tissue and asctrocyte cells. Downregulation of endogenous CUEDC2 in glioma U251 cell lines by RNAi promoted the tumor cells proliferation, migration, invasion and glioma neurosphere formation, while, overexpression of CUEDC2 showed the opposite effect. Further studies showed that overexpression of CUEDC2 suppressed the activation and nuclear translocation of phosphorylated-STAT3 (p-STAT3) but the level of p-STAT3 increased after interfering with the expression of CUEDC2. Moreover, CUEDC2 expression has an inhibitory effect on the activation of NF-κB. Thus, our studies suggested that the decreased expression of CUEDC2 in glioma led to the activation of transcription factor STAT3 and NF-κB signaling pathway which may be related to the tumorigenicity in glioma.

摘要

CUEDC2 是一种含有 CUE 结构域的 2 蛋白,在许多生物学过程中发挥着关键作用,如细胞周期、炎症和肿瘤发生。然而,CUEDC2 是否参与了胶质瘤的肿瘤发生以及可能的机制仍有待阐明。在本研究中,我们的结果表明,CUEDC2 在胶质瘤组织和胶质瘤细胞系中的表达低于正常组织和星形胶质细胞。通过 RNAi 下调胶质瘤 U251 细胞系中的内源性 CUEDC2 促进了肿瘤细胞的增殖、迁移、侵袭和胶质瘤神经球形成,而 CUEDC2 的过表达则表现出相反的效果。进一步的研究表明,CUEDC2 的过表达抑制了磷酸化 STAT3(p-STAT3)的激活和核易位,但干扰 CUEDC2 的表达后,p-STAT3 的水平增加。此外,CUEDC2 的表达对 NF-κB 的激活有抑制作用。因此,我们的研究表明,胶质瘤中 CUEDC2 的表达降低导致转录因子 STAT3 和 NF-κB 信号通路的激活,这可能与胶质瘤的致瘤性有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a679/5467786/d0e8bb6ccfac/IJO-51-01-0115-g00.jpg

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