MicroRNA-584-3p, a novel tumor suppressor and prognostic marker, reduces the migration and invasion of human glioma cells by targeting hypoxia-induced ROCK1.
MicroRNA-584-3p, a novel tumor suppressor and prognostic marker, reduces the migration and invasion of human glioma cells by targeting hypoxia-induced ROCK1.
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MicroRNA-584-3p是一种新型肿瘤抑制因子和预后标记物，通过靶向缺氧诱导的ROCK1来减少人胶质瘤细胞的迁移和侵袭
DOI：
10.18632/oncotarget.6735
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发表时间：
2016-01-26
期刊：
影响因子：
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通讯作者：
Li G
中科院分区：
文献类型：
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作者：
Xue H;Guo X;Han X;Yan S;Zhang J;Xu S;Li T;Guo X;Zhang P;Gao X;Liu Q;Li G
在这里，我们报告了microRNA-584-3p （miR-584-3p）在缺氧胶质瘤细胞和高级别人类胶质瘤肿瘤（WHO分级III-IV）中相对于常氧细胞和低级别肿瘤（WHO分级I-II）分别上调。miR-584-3p高表达的高级别胶质瘤患者术后生存时间较miR-584-3p低表达的患者明显延长。miR-584-3p可能作为一种有效的肿瘤抑制因子和恶性胶质瘤的预后生物标志物。然而，这些特性背后的分子机制仍然知之甚少。我们的机制研究表明，miR-584-3p通过破坏缺氧诱导的应激纤维形成来抑制胶质瘤细胞的迁移和侵袭。具体来说，我们发现ROCK1是胶质瘤细胞中miR-584-3p的直接和功能相关的靶点。我们的研究结果证明了miR-584-3p在胶质瘤中的肿瘤抑制功能，它通过拮抗缺氧诱导的rock1依赖性应激纤维的形成来抑制肿瘤细胞的迁移和侵袭。我们的研究结果对胶质瘤基因治疗具有潜在的意义，并表明miR-584-3p可能代表胶质瘤的预后指标。
Here, we report that microRNA-584-3p (miR-584-3p) is up-regulated in hypoxic glioma cells and in high-grade human glioma tumors (WHO grades III–IV) relative to normoxic cells and to low-grade tumors (WHO grades I–II), respectively. The postoperative survival time was significantly prolonged in the high-grade glioma patients with high miR-584-3p expression compared with those with low miR-584-3p expression. miR-584-3p may function as a potent tumor suppressor and as a prognostic biomarker for malignant glioma. However, the molecular mechanisms underlying these properties remain poorly understood. Our mechanistic studies revealed that miR-584-3p suppressed the migration and invasion of glioma cells by disrupting hypoxia-induced stress fiber formation. Specifically, we have found that ROCK1 is a direct and functionally relevant target of miR-584-3p in glioma cells. Our results have demonstrated a tumor suppressive function of miR-584-3p in glioma, in which it inhibits the migration and invasion of tumor cells by antagonizing hypoxia-induced, ROCK1-dependent stress fiber formation. Our findings have potential implications for glioma gene therapy and suggest that miR-584-3p could represent a prognostic indicator for glioma.