title: miRNA-145 is downregulated in atypical and anaplastic meningiomas and negatively regulates motility and proliferation of meningioma cells.
abstract: Meningiomas are frequent, mostly benign intracranial or spinal tumors. A small subset of meningiomas is characterized by histological features of atypia or anaplasia that are associated with more aggressive biological behavior resulting in increased morbidity and mortality. Infiltration into the adjacent brain tissue is a major factor linked to higher recurrence rates. The molecular mechanisms of progression, including brain invasion are still poorly understood. We have studied the role of micro-RNA 145 (miR-145) in meningiomas and detected significantly reduced miR-145 expression in atypical and anaplastic tumors as compared with benign meningiomas. Overexpression of miR-145 in IOMM-Lee meningioma cells resulted in reduced proliferation, increased sensitivity to apoptosis, reduced anchorage-independent growth and reduction of orthotopic tumor growth in nude mice as compared with control cells. Moreover, meningioma cells with high miR-145 levels had impaired migratory and invasive potential in vitro and in vivo. PCR-array studies of miR145-overexpressing cells suggested that collagen type V alpha (COL5A1) expression is downregulated by miR-145 overexpression. Accordingly, COL5A1 expression was significantly upregulated in atypical and anaplastic meningiomas. Collectively, our data indicate an important anti-migratory and anti-proliferative function of miR-145 in meningiomas.
authors.affiliation: Institute of Neuropathology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Kliese
authors.forename: P
authors.initials: P
authors.lastname: Gobrecht
authors.forename: D
authors.initials: D
authors.lastname: Pachow
authors.forename: N
authors.initials: N
authors.lastname: Andrae
authors.forename: A
authors.initials: A
authors.lastname: Wilisch-Neumann
authors.forename: E
authors.initials: E
authors.lastname: Kirches
authors.forename: M
authors.initials: M
authors.lastname: Riek-Burchardt
authors.forename: F
authors.initials: F
authors.lastname: Angenstein
authors.forename: G
authors.initials: G
authors.lastname: Reifenberger
authors.forename: M J
authors.initials: MJ
authors.lastname: Riemenschneider
authors.forename: E
authors.initials: E
authors.lastname: Meese
authors.forename: D
authors.initials: D
authors.lastname: Panayotova-Dimitrova
authors.forename: D H
authors.initials: DH
authors.lastname: Gutmann
authors.forename: C
authors.initials: C
authors.lastname: Mawrin
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation; D002455:Cell Division; D002465:Cell Movement; D024062:Collagen Type V / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation; D006801:Humans; D008577:Meningeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008579:Meningioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000503:physiopathology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009368:Neoplasm Transplantation; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014410:Tumor Stem Cell Assay
chemical_list: D024062:Collagen Type V; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C487931:mirnlet7 microRNA, human