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 Xue 1, 2 , Xing Guo 1, 2 , Xiao Han 1 , Shaofeng Yan 1 , Jinsen Zhang 1 , Shugang Xu 3 , Tong Li 1 , Xiaofan Guo 1 , Ping Zhang 1, 2 , Xiao Gao 1 , Qinglin Liu 1 , Gang Li 1, 2 1 Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China 2 Brain Science Research Institute, Shandong University, Jinan, Shandong Province, P.R. China 3 Department of Neurosurgery, Dezhou People’s Hospital, Dezhou, Shandong Province, P.R. China Correspondence to: Gang Li, e-mail: ligangqiluhospital@163.com Qinglin Liu, e-mail: bodystrong@126.com Keywords: microRNA, glioma, motility, hypoxia, prognosis Received: July 18, 2015      Accepted: November 26, 2015      Published: December 23, 2015 ABSTRACT 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.