title: Overexpression of miR-29a reduces the oncogenic properties of glioblastoma stem cells by downregulating Quaking gene isoform 6.
abstract: Glioblastoma is the most common type of malignant primary brain tumor and has high recurrence and lethality rates. Glioblastoma stem cells (GSCs), a subpopulation of glioblastoma cells, may promote rapid tumor recurrence and therapy resistance. Because altered microRNA (miR) expression in GSCs may lead to glioblastoma progression, we assessed the effects of miR-29a expression on the oncogenic behavior of GSCs. MiR-29a expression was lower in GSCs than non-GSCs, and overexpression of miR-29a in GSCs inhibited cell proliferation, migration and invasion, but promoted apoptosis. MiR-29a directly inhibited the expression of Quaking gene isoform 6 (QKI-6) by binding to its 3'-UTR, and thus inhibited GSC malignant behavior. In addition, Wilms' tumor 1-associating protein (WTAP) was identified as a downstream target of QKI-6. Overexpression of miR-29a in GSCs inhibited expression of WTAP and suppressed both phosphoinositide 3-kinase/AKT and extracellular signal-related kinase pathways by downregulating QKI-6, thereby inhibiting cell proliferation, migration, and invasion but promoting apoptosis. We have characterized a novel miR-29a/QKI-6/WTAP axis in GSCs, which may provide theoretical support for the treatment of glioblastoma with miR-29a agomirs.
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.|Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang 110004, People's Republic of China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Xi
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, People's Republic of China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Shang
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.|Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang 110004, People's Republic of China.
authors.forename: Xiaobai
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, People's Republic of China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.|Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang 110004, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.|Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang 110004, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Bao
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.|Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang 110004, People's Republic of China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D018797:Cell Cycle Proteins; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; C490832:QKI protein, human; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; C419554:WTAP protein, human
keywords: QKI-6; WTAP; glioblastoma stem cells; glioma; miR-29a