miR-93 promotes cell proliferation in gliomas through activation of PI3K/Akt signaling pathway.
miR-93 promotes cell proliferation in gliomas through activation of PI3K/Akt signaling pathway.
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miR-93 通过激活 PI3K/Akt 信号通路促进胶质瘤细胞增殖
DOI：
10.18632/oncotarget.3221
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发表时间：
2015-04-10
期刊：
影响因子：
--
通讯作者：
Song L
中科院分区：
文献类型：
--
作者：
Jiang L;Wang C;Lei F;Zhang L;Zhang X;Liu A;Wu G;Zhu J;Song L
PI 3 K/Akt信号通路在各种人类癌症类型中频繁激活，并在癌症的发展和进展中发挥重要作用。还发现多种调节剂，如磷酸酶和张力蛋白同源物（PTEN）和PH结构域富含亮氨酸重复蛋白磷酸酶（PHLPP），参与PI 3 K/Akt信号传导途径的抑制。然而，这些调节剂介导的抑制作用如何在显示组成性激活的PI 3 K/Akt信号传导的癌症中同时被破坏，仍然令人困惑。在本研究中，我们报道了miR-93在胶质瘤细胞系和临床胶质瘤组织中的表达显著上调。统计学分析显示，miR-93水平与胶质瘤的临床病理分级和总生存率显著相关。此外，我们发现过表达miR-93促进胶质瘤细胞增殖和细胞周期进程，但抑制miR-93则降低。我们证明miR-93通过靶向PTEN、PHLPP 2和FOXO 3的3′ UTR直接抑制其表达来激活PI 3 K/Akt信号通路。因此，我们的研究结果表明，miR-93可能在胶质瘤的进展中发挥重要作用，并揭示了胶质瘤中组成性PI 3 K/Akt激活的新机制。
The PI3K/Akt signaling pathway is frequently activated in various human cancer types and plays essential roles in development and progression of cancers. Multiple regulators, such as phosphatase and tensin homolog (PTEN) and PH domain leucine rich repeat protein phosphatases (PHLPP), have also found to be involved in suppression of the PI3K/Akt signaling pathway. However, how suppressive effects mediated by these regulators are concomitantly disrupted in cancers, which display constitutively activated PI3K/Akt signaling, remains puzzling. In the present study, we reported that the expression of miR-93 was markedly upregulated in glioma cell lines and clinical glioma tissues. Statistical analysis revealed that miR-93 levels significantly correlated with clinicopathologic grade and overall survival in gliomas. Furthermore, we found that overexpressing miR-93 promoted, but inhibition of miR-93 reduced, glioma cell proliferation and cell-cycle progression. We demonstrated that miR-93 activated PI3K/Akt signaling through directly suppressing PTEN, PHLPP2 and FOXO3 expression via targeting their 3′UTRs. Therefore, our results suggest that miR-93 might play an important role in glioma progression and uncover a novel mechanism for constitutive PI3K/Akt activation in gliomas.
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