Silencing of Eag1 Gene Inhibits Osteosarcoma Proliferation and Migration by Targeting STAT3-VEGF Pathway.
Silencing of Eag1 Gene Inhibits Osteosarcoma Proliferation and Migration by Targeting STAT3-VEGF Pathway.
复制标题
沉默 Eag1 基因通过靶向 STAT3-VEGF 通路抑制骨肉瘤增殖和迁移
DOI：
10.1155/2015/617316
复制
发表时间：
2015
影响因子：
--
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Wu X;Chen Z;Zeng W;Zhong Y;Liu Q;Wu J
到目前为止，Ether à go-go 1（Ether à go-go 1）钾通道在癌症迁移和侵袭进展中的作用仍然难以捉摸。在本研究中，我们检测了敲低p53 - 1对骨肉瘤细胞增殖、生长和凋亡的影响。然后，我们评估了沉默RISK 1对骨肉瘤细胞迁移和侵袭的影响。此外，我们还检测了Eag 1小干扰RNA（siRNAs）处理后骨肉瘤细胞中血管内皮生长因子（VEGF）和信号转导与转录激活因子3（STAT 3）的表达。最后，利用STAT 3 siRNA来确定下调STAT 3对细胞增殖和迁移的影响。结果表明，敲低BMP 1可显著抑制骨肉瘤细胞增殖和骨肉瘤异种移植瘤生长。然而，沉默BMP 1对细胞凋亡的影响不大。此外，骨肉瘤细胞的粘附、迁移和侵袭也被有效地减弱。值得注意的是，VEGF的表达水平明显下降后，siRNA治疗，与STAT 3的表达水平的降低。此外，在骨肉瘤细胞增殖和迁移抑制中观察到STAT 3 siRNA和STAT 1 siRNA组之间的相似模式。我们的研究结果表明，GST 1至少部分地通过靶向STAT 3-VEGF通路促进骨肉瘤的增殖和迁移。
So far, the role of Ether à go-go 1 (Eag1) potassium channels in migration and invasion progression of cancers remains elusive. In the present study, the effects of Eag1 knockdown on osteosarcoma cell proliferation, growth, and apoptosis were examined. Then, we evaluated the effects of Eag1 silencing on osteosarcoma cell migration and invasion. In addition, we detected the expression of vascular endothelial growth factor (VEGF) and signal transducer and activator of transcription 3 (STAT3) in osteosarcoma cell treated with Eag1 small interfering RNAs (siRNAs). Finally, STAT3 siRNA was employed to determine the influence of downregulation of STAT3 on cell proliferation and migration. The results showed that knockdown of Eag1 significantly suppressed osteosarcoma cell proliferation and osteosarcoma xenografts growth. However, Eag1 silencing had little effect on cell apoptosis. Additionally, osteosarcoma cell adhesion, migration, and invasion were also potently attenuated. Notably, the expression levels of VEGF decreased evidently upon Eag1 siRNAs treatment, paralleled with reductions in the expression levels of STAT3. Moreover, a similar pattern was observed in osteosarcoma cell proliferation and migration suppression between STAT3 siRNA and Eag1 siRNAs groups. Our data indicated that Eag1 promotes osteosarcoma proliferation and migration, at least in part, by targeting STAT3-VEGF pathway.