MicroRNA-584-3p, a novel tumor suppressor and prognostic marker, reduces the migration and invasion of human glioma cells by targeting hypoxia-induced ROCK1

被引:40
|
作者
Xue, Hao [1 ,2 ]
Guo, Xing [1 ,2 ]
Han, Xiao [1 ]
Yan, Shaofeng [1 ]
Zhang, Jinsen [1 ]
Xu, Shugang [3 ]
Li, Tong [1 ]
Guo, Xiaofan [1 ]
Zhang, Ping [1 ,2 ]
Gao, Xiao [1 ]
Liu, Qinglin [1 ]
Li, Gang [1 ,2 ]
机构
[1] Shandong Univ, Qilu Hosp, Dept Neurosurg, Jinan 250100, Shandong, Peoples R China
[2] Shandong Univ, Brain Sci Res Inst, Jinan 250100, Shandong, Peoples R China
[3] Dezhou Peoples Hosp, Dept Neurosurg, Dezhou, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
microRNA; glioma; motility; hypoxia; prognosis; BRAIN-TUMORS; STEM-CELLS; GLIOBLASTOMA-MULTIFORME; ACTIVATED MICRORNA; SELF-RENEWAL; CANCER-CELLS; ANGIOGENESIS; EXPRESSION; GROWTH; PROLIFERATION;
D O I
10.18632/oncotarget.6735
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:4785 / 4805
页数:21
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