title: MicroRNA-584-3p, a novel tumor suppressor and prognostic marker, reduces the migration and invasion of human glioma cells by targeting hypoxia-induced ROCK1.
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.
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.|Brain Science Research Institute, Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xue
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.|Brain Science Research Institute, Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Xing
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Shaofeng
authors.initials: S
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Jinsen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Dezhou People's Hospital, Dezhou, Shandong Province, P.R. China.
authors.forename: Shugang
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.|Brain Science Research Institute, Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.|Brain Science Research Institute, Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C552781:MIRN584 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases
keywords: glioma; hypoxia; microRNA; motility; prognosis