Abstract
Runt-related transcription factor 1 (RUNX1) is essential for the establishment of fetal and adult hematopoiesis and neuronal development. Aberrant expression of RUNX1 led to proliferation and metastasis of several cancers. The aim of the present study was to investigate the role of RUNX1 in migration, invasion, and angiogenesis of human glioblastoma using IL-1β-treated U-87 MG human glioblastoma cells as a model. IL-1β at 10 ng/ml stimulated translocation of RUNX1 into the nucleus with increased expressions of RUNX1, MMP-1, MMP-2, MMP-9, MMP-19, and VEGFA in U-87 MG cells. In addition, silencing of RUNX1 gene significantly suppressed U-87 MG cell migration and invasion abilities. Moreover, knockdown of RUNX1 mRNA in U-87 MG cells reduced the tube formation of human umbilical vein endothelial cells. Further investigation revealed that IL-1β-induced RUNX1 expression might be mediated via the p38 mitogen-activated protein kinase (MAPK) signaling molecule for the expression of these invasion- and angiogenic-related molecules. Together with an inhibitor of p38 MAPK (SB203580) could decrease RUNX1 mRNA expression. Thus, RUNX1 may be one of the putative molecular targeted therapies against glioma metastasis and angiogenesis through the activation of p38 MAPK signaling pathway.
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Acknowledgements
This work is supported by the grants from Faculty of Science, Mahidol University, Thailand to Kulathida Chaithirayanon; Service Support Category, Department of Medical Services, Ministry of Public Health, Thailand to Pornpun Vivithanaporn; and the National Research Council of Thailand to Kant Sangpairoj.
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Sangpairoj, K., Vivithanaporn, P., Apisawetakan, S. et al. RUNX1 Regulates Migration, Invasion, and Angiogenesis via p38 MAPK Pathway in Human Glioblastoma. Cell Mol Neurobiol 37, 1243–1255 (2017). https://doi.org/10.1007/s10571-016-0456-y
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DOI: https://doi.org/10.1007/s10571-016-0456-y