RUNX2 promotes gastric cancer progression through the transcriptional activation of MGAT5 and MMP13
4
Citation
29
Reference
10
Related Paper
Citation Trend
Abstract:
RUNX2 is overexpressed in gastric cancer but the mechanism(s) through which it promotes tumor progression remain undefined. Here, we investigated the role of RUNX2 on gastric cancer pathogenesis at the molecular level.The qRT-PCR and western bolt were utilized to examine the mRNA and protein levels. CCK-8, Transwell and wound healing assays were used to measure cell proliferation, invasion and migration. CHIP-PCR gel electrophoresis was used to verify RUNX2 as a transcription factor for MMP13 and MGAT5. The in vivo assay was utilized to assess tumor growth. In vivo assay was used to evaluate tumor growth, aberrant expression of RUNX2 and lung metastasis of gastric cancer.RUNX2 is overexpressed in MKN-45 and AGS cells. Genetic RUNX2 silencing reduced the proliferation, invasion and migration of MKN-45 and AGS cells. Analysis of the gastric cancer samples from the database revealed a significant positive correlation between MGAT5, MMP13, and RUNX2 expression. JASPAR analysis revealed that there was a potential binding site of RUNX2 in the promoter regions of MGAT5 and MMP13, and the experimental results confirmed that RUNX2 could regulate the expression of MGAT5 and MMP13 respectively. In vivo assays confirmed the aberrant expression of RUNX2 in mouse models of gastric cancer and reduced growth and lung metastasis in RUNX2 silenced xenograft tumors assessed.Collectively, these data reveal that RUNX2 enhances MGAT5 and MMP13 expression in gastric cancer cells and represents a biomarker and potential therapeutic target for gastric cancer therapy.Keywords:
RUNX2
Occlusal force is an important stimulus for maintaining periodontal homeostasis. This is attributed to the quality of human periodontal ligament fibroblasts (hPDLFs) that could transfer occlusal force into biological signals modulating osteoblst differentiation. However, few studies investigated the mechanism of occlusal force‐induced osteodifferentiation of hPDLFs. In our study, we used the cyclic mechanical tension (CMT) at 10% elongation with 0.5 Hz to mimic occlusal force, and explored its effects on osteogenesis of hPDLFs. Firstly, elevated expressions of several osteoblast marker genes (Runx2, ATF4, SP7, OCN, and BSP), as well as activated ERK1/2 pathway were detected during CMT loading for 1, 3, 6, 12, 18, and 24 h. To gain further insight into how CMT contributed to those effects, we focused on the classic ERK1/2‐Runx2 pathway by inhibiting ERK1/2 and overexpressing Runx2. Our results reflected that Runx2 overexpression alone could induce osteodifferentiation of hPDLFs. Meanwhile, CMT loading could intensify while combined ERK1/2 blockage could weaken this process. Furthermore, we found that CMT promoted Runx2 transcription and phosphorylation via ERK1/2; protein level of phospho‐Runx2 (p‐Runx2), rather than Runx2, was in parallel with mRNA expressions of SP7, OCN, and BSP. Taken together, our study proved that p‐Runx2, elevated by CMT via ERK1/2 pathway, is the predominate factor in promoting osteoblast differentiation of hPDLFs. J. Cell. Physiol. 230: 2426–2436, 2015. © 2015 Wiley Periodicals, Inc.
RUNX2
Periodontal fiber
Cite
Citations (40)
Runt-related transcription factor 2 (RUNX2) is a transcription factor closely associated with the osteoblast phenotype. While frequently referred to, the complexity of its regulation and its interactions within the osteoblast differentiation pathway are often overlooked. This review aims to summarise the knowledge of its regulation at the transcriptional, translational and post-translational level. In addition, the regulation of RUNX2 by factors commonly used during osteogenic studies will be discussed.
RUNX2
Cite
Citations (524)
The dysfunction of osteogenesis is a key character in the pathogenesis of osteoporosis, but the network of signaling mechanisms in controlling the differentiation of osteoblast remain unclear. Thrap3 has been proved participating in various biological process, especially in the differentiation of stem cells. Here, we demonstrate that Thrap3 could promote osteogenesis through the inhibition of the degradation of Runx2, which is a key molecular structure in early osteoblast differentiation. Furthermore, we found that the osteogenesis enhancing capacity of Thrap3 was caused by physically binding with Sox9, inhibiting the transcriptional activity of Sox9, and then decreasing the decomposition-promoted effect of Sox9 on Runx2. Our data shows that Thrap3 promotes osteoblast differentiation through the Thrap3-Sox9-Runx2 axis. What we found may help for further clarifying the molecular mechanism of osteogenic differentiation and give a new potential therapeutic target for osteoporosis.
RUNX2
SOX9
Bone Formation
Cite
Citations (7)
VGLL4 relieves TEADs-mediated RUNX2 transcriptional inhibition by impairing TEADs-RUNX2 interaction.
RUNX2
Cleidocranial Dysplasia
Cite
Citations (50)
RUNX2
AP-1 transcription factor
Transcription
GATA transcription factor
Cite
Citations (373)
RUNX2
Cite
Citations (9)
RUNX2
Mechanotransduction
Cleidocranial Dysplasia
Cite
Citations (119)
RUNX2
Transcription
Morpholino
Cite
Citations (29)
RUNX2
Cite
Citations (470)