title: miR-200a-mediated suppression of non-muscle heavy chain IIb inhibits meningioma cell migration and tumor growth in vivo.
abstract: miR-200a has been implicated in the pathogenesis of meningiomas, one of the most common central nervous system tumors in humans. To identify how miR-200a contributes to meningioma pathogenesis at the molecular level, we used a comparative protein profiling approach using Gel-nanoLC-MS/MS and identified approximately 130 dysregulated proteins in miR-200a-overexpressing meningioma cells. Following the bioinformatic analysis to identify potential genes targeted by miR-200a, we focused on the non-muscle heavy chain IIb (NMHCIIb), and showed that miR-200a directly targeted NMHCIIb. Considering the key roles of NMHCIIb in cell division and cell migration, we aimed to identify whether miR-200a regulated these processes through NMHCIIb. We found that NMHCIIb overexpression partially rescued miR-200a-mediated inhibition of cell migration, as well as cell growth in vitro and in vivo. Moreover, siRNA-mediated silencing of NMHCIIb expression resulted in a similar migration phenotype in these cells and inhibited meningioma tumor growth in mice. Taken together, these results suggest that NMHCIIb might serve as a novel therapeutic target in meningiomas.
authors.affiliation: Department of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: O
authors.initials: O
authors.lastname: Senol
authors.affiliation: OncoProteomics Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: T B M
authors.initials: TB
authors.lastname: Schaaij-Visser
authors.affiliation: Molecular Neuro-Oncology Research Unit, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: E P
authors.initials: EP
authors.lastname: Erkan
authors.affiliation: Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Dorfer
authors.affiliation: Experimental Therapeutics and Molecular Imaging Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Lewandrowski
authors.affiliation: OncoProteomics Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: T V
authors.initials: TV
authors.lastname: Pham
authors.affiliation: OncoProteomics Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: S R
authors.initials: SR
authors.lastname: Piersma
authors.affiliation: Department of Neurosurgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: S M
authors.initials: SM
authors.lastname: Peerdeman
authors.affiliation: Institute of Neurology, Medical University of Vienna, Vienna, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Ströbel
authors.affiliation: Experimental Therapeutics and Molecular Imaging Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Tannous
authors.affiliation: Molecular Neuro-Oncology Research Unit, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: N
authors.initials: N
authors.lastname: Saydam
authors.affiliation: Molecular Neuro-Oncology Research Unit, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Slavc
authors.affiliation: Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.
authors.forename: E
authors.initials: E
authors.lastname: Knosp
authors.affiliation: OncoProteomics Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: C R
authors.initials: CR
authors.lastname: Jimenez
authors.affiliation: Molecular Neuro-Oncology Research Unit, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: O
authors.initials: O
authors.lastname: Saydam
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008577:Meningeal Neoplasms / Q000235:genetics / Q000473:pathology*; D008579:Meningioma / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D009368:Neoplasm Transplantation; D024501:Nonmuscle Myosin Type IIB / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering; D014183:Transplantation, Heterologous
chemical_list: C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains