CUEDC2 suppresses glioma tumorigenicity by inhibiting the activation of STAT3 and NF-κB signaling pathway.
CUEDC2 suppresses glioma tumorigenicity by inhibiting the activation of STAT3 and NF-κB signaling pathway.
复制标题
CUEDC2通过抑制STAT3和NF-κB信号通路的激活来抑制胶质瘤致瘤性
DOI：
10.3892/ijo.2017.4009
复制
发表时间：
2017-07
影响因子：
5.2
通讯作者：
Gao D
中科院分区：
文献类型：
--
作者：
Li F;Tang C;Jin D;Guan L;Wu Y;Liu X;Wu X;Wu QY;Gao D
CUEDC2是一个含有2蛋白的CUE结构域，在细胞周期、炎症和肿瘤发生等许多生物过程中起着重要作用。然而，CUEDC2是否参与胶质瘤的发生及其可能的机制尚不清楚。在本研究中，我们的研究结果表明，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胶质细胞。通过RNAi下调胶质瘤U251细胞系内源性CUEDC2可促进肿瘤细胞的增殖、迁移、侵袭及胶质瘤神经球的形成，而过表达CUEDC2则相反。进一步研究表明，CUEDC2过表达可抑制磷酸化stat3 （p-STAT3）的活化和核易位，但干扰CUEDC2表达后，p-STAT3水平升高。CUEDC2的表达对NF-κB的活化有抑制作用。因此，我们的研究提示，CUEDC2在胶质瘤中的表达降低，导致转录因子STAT3和NF-κB信号通路的激活，可能与胶质瘤的致瘤性有关。
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.