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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Hao Xue1,2, Xing Guo1,2, Xiao Han1, Shaofeng Yan1, Jinsen Zhang1, Shugang Xu3, Tong Li1, Xiaofan Guo1, Ping Zhang1,2, Xiao Gao1, Qinglin Liu1, Gang Li1,2
1Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China
2Brain Science Research Institute, Shandong University, Jinan, Shandong Province, P.R. China
3Department of Neurosurgery, Dezhou People’s Hospital, Dezhou, Shandong Province, P.R. China
Gang Li, e-mail: [email protected]
Qinglin Liu, e-mail: [email protected]
Keywords: microRNA, glioma, motility, hypoxia, prognosis
Received: July 18, 2015 Accepted: November 26, 2015 Published: December 23, 2015
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.
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