title: miR340 suppresses the stem-like cell function of glioma-initiating cells by targeting tissue plasminogen activator.
abstract: Glioma-initiating cells (GIC) have stem-like cell properties thought to be sufficient for recurrence, progression, and drug resistance in glioblastomas. In the present study, we defined miRNA (miR)-340 as a differentially expressed miRNA in human GICs that inhibit GIC-mediated tumorigenesis. Furthermore, we defined tissue plasminogen activator (PLAT) as a critical direct target of miR340 for inhibition. Among miRNAs screened, we found that miR340 expression was decreased in all human GICs and in human glioblastoma tissues, compared with human neural stem cells and normal brain tissues. miR340 overexpression in GICs suppressed their proliferative, invasive, and migratory properties in vitro, triggering cell senescence in vitro and inhibiting GIC-induced tumorigenesis in mouse brains. shRNA-mediated silencing of PLAT in GICs phenocopied the effects of miR340 overexpression in vitro and in vivo, suggesting a potential role for tissue factor in stem-like cell function. Taken together, our results identified miR340 as a tumor suppressor that functions in GIC to enforce PLAT blockade and ablate their stem-like functions.
authors: Department of Neurosurgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors: Daisuke
authors: D
authors: Yamashita
authors: Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors: Toru
authors: T
authors: Kondo
authors: Department of Neurosurgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. sohue@m.ehime-u.ac.jp.
authors: Shiro
authors: S
authors: Ohue
authors: Department of Molecular and Cellular Physiology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors: Hisaaki
authors: H
authors: Takahashi
authors: DNA Chip Research Inc., Yokohama, Kanagawa, Japan.
authors: Madoka
authors: M
authors: Ishikawa
authors: DNA Chip Research Inc., Yokohama, Kanagawa, Japan.
authors: Ryo
authors: R
authors: Matoba
authors: Department of Neurosurgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors: Satoshi
authors: S
authors: Suehiro
authors: Department of Neurosurgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors: Shohei
authors: S
authors: Kohno
authors: Department of Neurosurgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors: Hironobu
authors: H
authors: Harada
authors: Department of Molecular and Cellular Physiology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors: Junya
authors: J
authors: Tanaka
authors: Department of Neurosurgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors: Takanori
authors: T
authors: Ohnishi
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005910:Glioma / Q000473:pathology*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000502:physiology*; D010959:Tissue Plasminogen Activator / Q000235:genetics* / Q000502:physiology
chemical_list: C570046:MIRN340 microRNA, human; D035683:MicroRNAs; D010959:Tissue Plasminogen Activator