miR-200a-mediated suppression of non-muscle heavy chain IIb inhibits meningioma cell migration and tumor growth in vivo

Autor: Bakhos A. Tannous, Saskia M. Peerdeman, Ozlem Senol, Engelbert Knosp, Erdogan Pekcan Erkan, Grant K. Lewandrowski, Sander R. Piersma, Thang V. Pham, Irene Slavc, Nurten Saydam, Thomas Ströbel, Christian Dorfer, Tieneke B M Schaaij-Visser, Connie R. Jimenez, Okay Saydam
Přispěvatelé: Medical oncology laboratory, Neurosurgery, CCA - Innovative therapy
Rok vydání: 2015
Předmět:
Zdroj: Senol, O, Schaaij-Visser, T B M, Erkan, E P, Dorfer, C, Lewandrowski, G, Pham, T V, Piersma, S R, Peerdeman, S M, Strobel, T, Tannous, B, Saydam, N, Slavc, I, Knosp, E, Jimenez, C R & Saydam, O 2015, ' miR-200a-mediated suppression of non-muscle heavy chain IIb inhibits meningioma cell migration and tumor growth in vivo ', Oncogene, vol. 34, no. 14, pp. 1790-1798 . https://doi.org/10.1038/onc.2014.120
Oncogene, 34(14), 1790-1798. Nature Publishing Group
ISSN: 0950-9232
DOI: 10.1038/onc.2014.120
Popis: 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.
Databáze: OpenAIRE