Downregulation of angiogenin inhibits the growth and induces apoptosis in human bladder cancer cells through regulating AKT/mTOR signaling pathway
Downregulation of angiogenin inhibits the growth and induces apoptosis in human bladder cancer cells through regulating AKT/mTOR signaling pathway
复制标题
下调血管生成素通过调节AKT/mTOR信号通路抑制人膀胱癌细胞生长并诱导细胞凋亡
DOI：
10.1007/s10735-014-9608-x
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发表时间：
2015-04-01
影响因子：
3.2
通讯作者：
Chen, Junxia
中科院分区：
文献类型：
--
作者：
Shu, Jing;Huang, Mengge;Chen, Junxia
血管生成素（ANG）是一种多功能分泌蛋白，属于胰腺核糖核酸酶A超家族，被认为在细胞存活、生长和增殖中发挥比介导血管生成更重要的作用。越来越多的证据表明，ANG的表达和活性在多种人类癌症中显着增加。最近的研究表明，ANG 通过内皮细胞上的假定受体激活细胞信号通路。然而，其根本机制仍然很大程度上未知。 AKT/mTOR 信号通路参与细胞生长、细胞周期进程和细胞凋亡。我们研究的目的是确定ANG是否通过调节AKT/mTOR信号通路参与膀胱癌细胞的生长和转移。在本研究中，我们构建了 ANG siRNA 质粒，转染人膀胱癌 T24 细胞。我们证明了 ANG 的敲低可以抑制细胞增殖、调节细胞周期并诱导细胞凋亡。我们还发现 ANG 的下调显着降低了信号靶标 AKT、GSK-3β 和 mTOR 的磷酸化。此外，ANG 的下调会增加核糖核酸酶抑制剂的表达，核糖核酸酶抑制剂是一种具有多种功能的细胞质酸性蛋白。最后，ANG siRNA 抑制体内肿瘤发生和转移。总而言之，这些发现首次强调 ANG 可以通过调节 AKT/mTOR 信号通路在膀胱癌的发展中发挥关键作用。 ANG 和相关因子的靶向可以提供抑制人类膀胱癌的新策略。
Angiogenin (ANG) is a multifunctional secreted protein that belongs to the pancreatic ribonuclease A super family, which has been conceived to play a more important role in cell survival, growth and proliferation than the mediation of angiogenesis. Accumulating evidences suggest that the expression and activity of ANG increased significantly in a variety of human cancers. Recent studies showed that ANG activates cell signaling pathway through the putative receptor on endothelial cells. However, the underlying mechanisms remain largely unknown. AKT/mTOR signaling pathway participates in cell growth, cell-cycle progression and cell apoptosis. The purpose of our study was to determine whether ANG implicated in growth and metastasis of bladder cancer cells through regulating AKT/mTOR signaling pathway. In this study, we constructed ANG siRNA plasmids that transfected into human bladder cancer T24 cells. We demonstrated that knockdown of ANG could inhibit cell proliferation, regulate cell cycle and induce apoptosis. We also found that down-regulation of ANG remarkably reduced the phosphorylation of signaling targets AKT, GSK-3β and mTOR. Furthermore, down-regulation of ANG increased expression of ribonuclease inhibitor, which is a cytoplasmic acidic protein with many functions. Finally, ANG siRNA led to the suppression for tumorigenesis and metastasis in vivo. Taken together, these findings highlight for the first time that ANG could play a pivotal role in the development of bladder cancer through regulating AKT/mTOR signaling pathway. The targeting of ANG and associated factors could provide a novel strategy to inhibit human bladder cancer.