scholarly journals EGR2-mediated regulation of m6A reader IGF2BP proteins drive RCC tumorigenesis and metastasis via enhancing S1PR3 mRNA stabilization

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Yufan Ying ◽  
Xueyou Ma ◽  
Jiajie Fang ◽  
Shiming Chen ◽  
Weiyu Wang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Growth Response ◽  
Bioinformatics Analysis ◽  
Cell Cancer ◽  
Early Growth ◽  
Luciferase Reporter ◽  
Early Growth Response ◽  
Reporter Assays

AbstractEmerging discoveries of dynamic and reversible N6-methyladenosine (m6A) modification on RNA in mammals have revealed the key roles of the modification in human tumorigenesis. As known m6A readers, insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) are upregulated in most cancers and mediates the enhancement of m6A-modified mRNAs stability. However, the mechanisms of IGF2BPs in renal cell cancer (RCC) still remain unclear. Bioinformatic analysis and RT-qPCR were performed to evaluate the expression of IGF2BPs and m6A writer Wilms tumor 1-associating protein (WTAP) in RCC samples and its correlation with patient prognosis. In vitro, in vivo biological assays were performed to investigate the functions of IGF2BPs and WTAP in RCC. Chromatin immunoprecipitation-qPCR (ChIP-qPCR) combined with bioinformatics analysis and following western blot assay, dual-luciferase reporter assays were performed to validate the regulatory relationships between transcription factor (TF) early growth response 2 (EGR2) and potential target genes IGF2BPs. RNA sequencing (RNA-seq), methylated RNA immunoprecipitation-qPCR (MERIP-qPCR), RIP-qPCR, m6A dot blot, and dual-luciferase reporter assays combined with bioinformatics analysis were employed to screen and validate the direct targets of IGF2BPs and WTAP. Here, we showed that early growth response 2 (EGR2) transcription factor could increase IGF2BPs expression in RCC. IGF2BPs in turn regulated sphingosine-1-phosphate receptor 3 (S1PR3) expression in an m6A-dependent manner by enhancing the stability of S1PR3 mRNA. They also promoted kidney tumorigenesis via PI3K/AKT pathway. Furthermore, IGF2BPs and WTAP upregulation predicted poor overall survival in RCC. Our studies showed that the EGR2/IGF2BPs regulatory axis and m6A-dependent regulation of S1PR3-driven RCC tumorigenesis, which enrich the m6A-modulated regulatory network in renal cell cancer. Together, our findings provide new evidence for the role of N6-methyladenosine modification in RCC.

scholarly journals Toxoplasma gondii Rhoptry Discharge Correlates with Activation of the Early Growth Response 2 Host Cell Transcription Factor

2008 ◽  
Vol 76 (10) ◽  
pp. 4703-4712 ◽  
Author(s):  
Eric D. Phelps ◽  
Kristin R. Sweeney ◽  
Ira J. Blader
Keyword(s):  
Transcription Factor ◽  
Toxoplasma Gondii ◽  
Host Cell ◽  
Growth Response ◽  
Neospora Caninum ◽  
Early Growth ◽  
Apicomplexan Parasite ◽  
Host Cells ◽  
Early Growth Response ◽  
Cell Extracts

ABSTRACT Toxoplasma gondii is a ubiquitous apicomplexan parasite that can cause severe disease in fetuses and immune-compromised patients. Rhoptries, micronemes, and dense granules, which are secretory organelles unique to Toxoplasma and other apicomplexan parasites, play critical roles in parasite growth and virulence. To understand how these organelles modulate infected host cells, we sought to identify host cell transcription factors triggered by their release. Early growth response 2 (EGR2) is a host cell transcription factor that is rapidly upregulated and activated in Toxoplasma-infected cells but not in cells infected with the closely related apicomplexan parasite Neospora caninum. EGR2 upregulation occurred only when live parasites were in direct contact with the host cell and not from exposure to cell extracts that contain dense granule or micronemal proteins. When microneme-mediated attachment was blocked by pretreating parasites with a calcium chelator, EGR2 expression was significantly reduced. In contrast, when host cells were infected with parasites in the presence of cytochalasin D, which allows rhoptry secretion but prevents parasite invasion, EGR2 was activated. Finally, we demonstrate that Toxoplasma activation of host p38 mitogen-activated protein kinase is necessary but not sufficient for EGR2 activation. Collectively, these data indicate that EGR2 is specifically upregulated by a parasite-derived secreted factor that is most likely a resident rhoptry protein.

scholarly journals Transcription Factor Early Growth Response 3 Is Associated with the TGF-β1 Expression and the Regulatory Activity of CD4-Positive T Cells In Vivo

2013 ◽  
Vol 191 (5) ◽  
pp. 2351-2359 ◽  
Author(s):  
Shuji Sumitomo ◽  
Keishi Fujio ◽  
Tomohisa Okamura ◽  
Kaoru Morita ◽  
Kazuyoshi Ishigaki ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
Growth Response ◽  
Early Growth ◽  
Regulatory Activity ◽  
Early Growth Response ◽  
Tgf Β1

The differential expression of the blood group P1 -A4GALT and P2 -A4GALT alleles is stimulated by the transcription factor early growth response 1

Transfusion ◽  
2018 ◽  
Vol 58 (4) ◽  
pp. 1054-1064 ◽  
Author(s):  
Chih-Chun Yeh ◽  
Ching-Jin Chang ◽  
Yuh-Ching Twu ◽  
Shu-Ting Hung ◽  
Yi-Jui Tsai ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Differential Expression ◽  
Blood Group ◽  
Growth Response ◽  
Early Growth ◽  
Early Growth Response ◽  
Early Growth Response 1

scholarly journals Lytic HSV-1 infection induces the multifunctional transcription factor Early Growth Response-1 (EGR-1) in rabbit corneal cells

2011 ◽  
Vol 8 (1) ◽  
pp. 262 ◽  
Author(s):  
Gautam R Bedadala ◽  
Jayavardhana R Palem ◽  
Lorna Graham ◽  
James M Hill ◽  
Harris E McFerrin ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Growth Response ◽  
Early Growth ◽  
Early Growth Response ◽  
Corneal Cells ◽  
Early Growth Response 1 ◽  
Multifunctional Transcription Factor ◽  
Hsv 1

scholarly journals Insulin Inhibits the Pro-Inflammatory Transcription Factor Early Growth Response Gene-1 (Egr)-1 Expression in Mononuclear Cells (MNC) and Reduces Plasma Tissue Factor (TF) and Plasminogen Activator Inhibitor-1 (PAI-1) Concentrations

2002 ◽  
Vol 87 (3) ◽  
pp. 1419-1422 ◽  
Author(s):  
Ahmad Aljada ◽  
Husam Ghanim ◽  
Priya Mohanty ◽  
Neeti Kapur ◽  
Paresh Dandona
Keyword(s):  
Transcription Factor ◽  
Tissue Factor ◽  
Plasminogen Activator ◽  
Growth Response ◽  
Plasminogen Activator Inhibitor ◽  
Early Growth ◽  
Plasminogen Activator Inhibitor 1 ◽  
Early Growth Response ◽  
Activator Inhibitor ◽  
Pai 1

We have recently demonstrated that an infusion of a low dose of insulin reduces the intranuclear NF-κB (a pro-inflammatory transcription factor) content in MNC while also reducing the p;asma concentration of NF-κB dependent pro-inflammatory cytokines and adhesion molecules. We have now tested the effect of insulin on the pro-inflammatory transcription factor, early growth response-1 (Egr-1) and plasma concentration of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1), two major proteins whose expression is modulated by Egr-1. Insulin was infused at the rate of 2 IU/h in 5% dextrose (100 mL/h) and KCI (8 mmol/h) for 4 h in the fasting state in ten obese subjects. Blood samples were obtained at 0, 2, 4 and 6 h. MNC were isolated and their total homogenates and nuclear fractions were prepared and Egr-1 was measured by electrophoretic mobility shift assay (EMSA). Plasma TF and PAI-1 were assayed by ELISA. There was a significant fall in Egr-1 at 2 (66 ± 14% of basal level) and 4 h (47± 17% of the basal level; P<0.01). PAI-1 levels (basal = 100%) decreased significantly after insulin infusion at 2 h (57 ± 6.7% of the basal level) and at 4 h (58 ± 8.3% of the basal level; P<0.001). Plasma TF levels (basal = 100%) decreased to 76 ± 7.7% of the basal level at 2 h and to 85 ± 10.4% of the basal level at 4 h (P<0.05). Thus, insulin reduces intranuclear Egr-1 and the expression of TF and PAI-1. These data provide further evidence that insulin has an anti-inflammatory effect including the inhibition of TF and PAI-1 expression. These effects suggest a potential beneficial effect of insulin in thrombin formation and fibrinolysis in atherothrombosis.

scholarly journals Upregulation of the Neuron-Specific K+/Cl- Cotransporter Expression by Transcription Factor Early Growth Response 4

2006 ◽  
Vol 26 (52) ◽  
pp. 13463-13473 ◽  
Author(s):  
P. Uvarov ◽  
A. Ludwig ◽  
M. Markkanen ◽  
C. Rivera ◽  
M. S. Airaksinen
Keyword(s):  
Transcription Factor ◽  
Growth Response ◽  
Early Growth ◽  
Early Growth Response
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