Neoplasma. 2017;64(1):13-21. doi: 10.4149/neo_2017_102.
We report in this study that microRNA-584-3p (miR-584-3p) is related to the vasculogenic mimicry (VM) of human glioma cells. Unsurprisingly, the postoperative survival time was significantly prolonged in those glioma patients without VM phenomena compared with those with positive VM. miR-584-3p may function as a potent tumor suppressor by inhibiting VM of malignant glioma. However, the molecular mechanisms underlying these properties remain poorly understood. Our preliminary mechanistic studies revealed that miR-584-3p suppressed the VM by disturbing hypoxia-induced stress fiber formation and migration of glioma cells. Specifically, we defined ROCK1 as a potential functionally relevant target of miR-584-3p involved in this process in glioma cells. Our results demonstrate a tumor suppressor function for miR-584-3p in glioma, where it inhibits the VM of tumor cells by antagonizing hypoxia-induced ROCK1-dependent stress fiber formation. Our findings have potential implications for glioma gene therapy by targeting miR-584-3p and suggest that VM could represent a prognostic indicator for gliomas.
在这项研究中我们报告,微小 RNA-584-3p(miR-584-3p)与人类神经胶质瘤细胞的血管生成拟态(VM)有关。毫不奇怪,与 VM 阳性的胶质瘤患者相比,没有 VM 现象的胶质瘤患者的术后生存时间明显延长。miR-584-3p 可能通过抑制恶性神经胶质瘤的 VM 发挥强大的肿瘤抑制作用。然而,这些特性背后的分子机制仍知之甚少。我们的初步机制研究表明,miR-584-3p 通过干扰缺氧诱导的应激纤维形成和神经胶质瘤细胞的迁移来抑制 VM。具体而言,我们将 ROCK1 定义为 miR-584-3p 在神经胶质瘤细胞中参与这一过程的潜在功能相关靶标。我们的结果表明 miR-584-3p 在神经胶质瘤中具有肿瘤抑制功能,通过拮抗缺氧诱导的 ROCK1 依赖性应激纤维形成来抑制肿瘤细胞的 VM。我们的发现对针对 miR-584-3p 的神经胶质瘤基因治疗具有潜在意义,并表明 VM 可能代表神经胶质瘤的预后指标。