RUNX1 Regulates Migration, Invasion, and Angiogenesis via p38 MAPK Pathway in Human Glioblastoma

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.

Transcription Factor Runx1 Activates Opn to Promote Tumor Progression in Head and Neck Cancer

“…Similarly, other study has shown a positive correlation between RUNX1 and the MAPK signaling pathway in cancer [33]. Furthermore, we veri ed that these markers also appear to be neutralizing when RUNX1 overexpression and OPN knockdown coexist.…”

RUNX1: an emerging therapeutic target for cardiovascular disease

“… 47 , 76 Other inflammatory mediators with known links to RUNX1 include the pro-inflammatory cytokine IL-1β and the transcription factor TGF-β. Treatment of a human glioblastoma cell line with IL-1β was shown to up-regulate RUNX1 expression via the p38 MAPK cascade 77 and TGF-β has been shown to increase RUNX1 expression in a range of cell types including adult hippocampal precursor cells, 78 mesenchymal stem cells, CD4 T cells, and a mouse hepatocyte cell line. 79 , 80 Currently, the effects of these inflammatory mediators on RUNX1 expression in the myocardium remain unknown.…”

p38 promoted retinal micro-angiogenesis through up-regulated RUNX1 expression in diabetic retinopathy

“…Recent report shows that RUNX1 may be a putative molecular target of therapies against glioma metastasis and angiogenesis through the activation of p38 MAPK signaling pathway [21]. We measured the expression level of p38 in DR model and HG cell model.…”

“…RUNX3 plays a crucial role in definitive hematopoiesis, differentiation of T-and B-cell lineages, and neuronal development [19,20]. Recent report shows that RUNX1 may be a putative molecular target of therapies against glioma metastasis and angiogenesis that function through the activation of the p38 MAPK signaling pathway [21]. However, the relationship between p38 and RUNX1 in retinal micro-angiogenesis in diabetic retinopathy is still unknown.…”