MicroRNA-503 acts as a tumor suppressor in glioblastoma for multiple antitumor effects by targeting IGF-1R.
MicroRNA-503 acts as a tumor suppressor in glioblastoma for multiple antitumor effects by targeting IGF-1R.
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MicroRNA-503 在胶质母细胞瘤中充当肿瘤抑制因子，通过靶向 IGF-1R 发挥多种抗肿瘤作用
DOI：
10.3892/or.2013.2951
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发表时间：
2014-03
期刊：
影响因子：
4.2
通讯作者：
He X
中科院分区：
文献类型：
--
作者：
Zhang Y;Chen X;Lian H;Liu J;Zhou B;Han S;Peng B;Yin J;Liu W;He X
MicroRNA(MiRNA)通过调节癌细胞的存活、增殖和侵袭与多种类型的人类癌症有关。MicroRNA-503(miR-503)的异常表达已在几种癌症中被报道。然而，miR-503水平在人类多形性胶质母细胞瘤(GBM)中的潜在联系和潜在的调控机制仍不清楚。在本研究中，我们首次发现miR-503在GBM组织和细胞系(U251和U87 MG)中的表达显著低于正常脑组织。此外，我们的结果表明，在GBM细胞系中过表达miR-503不仅通过诱导G0/G1细胞周期停滞和凋亡来抑制细胞增殖，而且还抑制了癌细胞的迁移和肿瘤的侵袭。此外，通过计算分析和荧光素酶报告分析，我们确定胰岛素样生长因子-1(IGF-1R)受体mRNA是miR-503的真正靶点。值得注意的是，在GBM细胞中miR-503的上调抑制了内源性IGF-1R蛋白的表达。进一步的机制分析表明，miR-503的强制表达抑制了AKT的激活，提示miR-503对GBM细胞的抑瘤作用部分是通过磷脂酰肌醇3-激酶/AKT信号转导途径实现的。综上所述，本研究结果表明miR-503通过靶向IGF-1R抑制脑胶质瘤的发生和发展，从而为脑胶质瘤的诊断提供了一个新的证据支持的预后标志物。
microRNA (miRNA) dysregulation is associated with various types of human cancer by regulating cancer cell survival, proliferation and invasion. Aberrant expression of microRNA-503 (miR-503) has been reported in several cancer profiles. However, potential linkage of miR-503 levels and the underlying regulatory mechanisms in human glioblastoma multiforme (GBM) remain unclear. In the present study, we showed for the first time that the expression of miR-503 was significantly reduced in GBM tissues and cell lines (U251 and U87MG) relative to normal brain tissues. Furthermore, our results demonstrated that overexpression of miR-503 in GBM cell lines not only suppressed cell proliferation through inducing G0/G1 cell cycle arrest and apoptosis, but also inhibited cancer cell migration and tumor invasion. In addition, we identified insulin-like growth factor-1 (IGF-1R) receptor mRNA is a bona fide target of miR-503 by computational analysis followed by luciferase reporter assays. Of note, upregulation of miR-503 in GBM cells suppressed endogenous IGF-1R protein expression. Further mechanistic analysis revealed that forced expression of miR-503 inhibited AKT activation, suggesting the tumor suppressive effect of miR-503 in GBM cells is partially mediated by phosphatidylinositol 3-kinase/AKT signaling. Taken together, the results of the present study demonstrated that miR-503 is a tumor suppressor for GBM and a favorable factor against glioma progression through targeting IGF-1R, thus providing a new evidence-supported prognostic marker for GBM diagnosis.
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影响因子：
5.6
作者：
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