The Role of the Transcription Factor EGR1 in Cancer

Wang, Bin; Guo, Hanfei; Yu, Haojun; Chen, Yong; Xu, Hong‐Tao; Zhao, Gang

doi:10.3389/fonc.2021.642547

Cited by 137 publications

(112 citation statements)

References 92 publications

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“…Early growth response 1 (EGR1) is a controversial gene that is involved in growth, differentiation and apoptosis. The protein encoded by this gene belongs to the EGR family of zinc finger proteins [ 12 ]. EGR1 is induced by various growth factors, cytokines and stress stimulation, such as radiation and injury [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Regulation of GDF15 by EGR1 Promotes Head and Neck Cancer Progression through a Positive Feedback Loop

Jin

Jung

Lim

et al. 2021

IJMS

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Growth and differentiation factor 15 (GDF15), a divergent member of the transforming growth factor-β (TGF-β) superfamily, has been reported to be overexpressed in different kinds of cancer types. However, the function and mechanism of GDF15 in head and neck cancer (HNC) remains unclear. The Cancer Genome Atlas (TCGA) data show that the expression of GDF15 is significantly associated with tumor AJCC stage, lymph vascular invasion and tumor grade in HNC. In this study, we confirmed that knockdown of GDF15 attenuated: cell proliferation, migration and invasion via regulation of EMT through a canonical pathway; SMAD2/3 and noncanonical pathways; PI3K/AKT and MEK/ERK in HNC cell lines. Furthermore, we found that early growth response 1 (EGR1) was a transcription factor of GDF15. Interestingly, we also demonstrated that GDF15 could regulate the expression of EGR1, which meant a positive feedback loop occurred between these two factors. Moreover, combined inhibition of both GDF15 and EGR1 in a HNC mouse xenograft model showed significantly decreased tumor volume compared to inhibition of EGR1 or GDF15 alone. Our study showed that the GDF15–EGR1 signaling axis may be a good target in HNC patients.

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Section: Introductionmentioning

confidence: 99%

Transcriptional Regulation of GDF15 by EGR1 Promotes Head and Neck Cancer Progression through a Positive Feedback Loop

Jin

Jung

Lim

et al. 2021

IJMS

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“…Still, mdEMF and stEMF significantly elevated BIRC5 at several time points (on average by 4-fold) when compared to LPS-stimulated and non-exposed controls, thereby further strengthening pro-survival signaling in THP1 ( Figure 6 c). stEMF further upregulated the pro-inflammatory cytokine interleukin 18 ( IL18 ) alongside early growth response 1 ( EGR1 ), an important transcription factor with multifaceted roles in tumor formation and proliferation as well as inflammation ([ 47 , 48 ], Figure 6 d,e). The drastic increase of EGR1 even at wkEMF exposure measured at the 3 h time point, in particular, highlights the severe scope of potential downstream-regulated pathways and hence the breadth of potential responses induced even by wkEMF.…”

Section: Resultsmentioning

confidence: 99%

“…Perhaps our data already constitute a potential mechanistic explanation to reports on increased childhood leukemia upon residential EMF exposure, as BIRC5 promotes cell proliferation and constitutes an important biomarker to predict the clinical outcome in AML patients [ 45 ]. Similarly, EMF upregulated EGR1 expression, a multifaceted transcription factor that mediates proliferation but also inflammatory signaling [ 47 , 48 ], constituting another potential link to observed effects on inflammation.…”

Section: Discussionmentioning

confidence: 99%

Anti-Oxidative and Immune Regulatory Responses of THP-1 and PBMC to Pulsed EMF Are Field-Strength Dependent

Groiss

Lammegger

Brislinger

2021

IJERPH

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Innate immune cells react to electromagnetic fields (EMF) by generating reactive oxygen species (ROS), crucial intracellular messengers. Discrepancies in applied parameters of EMF studies, e.g., flux densities, complicate direct comparison of downstream anti-oxidative responses and immune regulatory signaling. We therefore compared the impact of different EMF flux densities in human leukemic THP1 cells and peripheral blood mononuclear cells (PBMC) of healthy donors to additionally consider a potential disparate receptivity based on medical origin. ROS levels increased in THP1 cells stimulated with lipopolysaccharide (LPS) after one hour of EMF exposure. Moreover, weak EMF mitigated the depletion of the reducing agent NAD(P)H in THP1. Neither of these effects occurred in PBMC. Landscaping transcriptional responses to varied EMF revealed elevation of the anti-oxidative enzymes PRDX6 (2-fold) and DHCR24 (6-fold) in THP1, implying involvement in lipid metabolism. Furthermore, our study confirmed anti-inflammatory effects of EMF by 6-fold increased expression of IL10. Strikingly, THP1 responded to weak EMF, while PBMC were primarily affected by strong EMF, yet with severe cellular stress and enhanced rates of apoptosis, indicated by HSP70 and caspase 3 (CASP3). Taken together, our results emphasize an altered susceptibility of immune cells of different origin and associate EMF-related effects with anti-inflammatory signaling and lipid metabolism.

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“…40,41 As transcription factors, EGR1, KLF4, MYC, and CEBPB also perform diverse transcriptional functions in many cell physiological functions and cellular processes. 42 -45 Overexpressed EGR1 in chondrocytes could accelerate chondrocyte hypertrophy, prevent COl2A1 expression, and promote the release of inflammatory factors, such as MMP9 and MMP13. 46 Notably, endoplasmic reticulum stress can kinetically control CEBPB isoforms in fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein D as a Potential Biomarker and Construction of a Transcriptional Regulatory-Immune Network Associated with Osteoarthritis by Weighted Gene Coexpression Network Analysis

Qin

Zhou

et al. 2021

CARTILAGE

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Objective Synovial inflammation influences the progression of osteoarthritis (OA). Herein, we aimed to identify potential biomarkers and analyze transcriptional regulatory-immune mechanism of synovitis in OA using weighted gene coexpression network analysis (WGCNA). Design A data set of OA synovium samples (GSE55235) was analyzed based on WGCNA. The most significant module with OA was identified and function annotation of the module was performed, following which the hub genes of the module were identified using Pearson correlation and a protein-protein interaction network was constructed. A transcriptional regulatory network of hub genes was constructed using the TRRUST database. The immune cell infiltration of OA samples was evaluated using the single-sample Gene Set Enrichment Analysis (ssGSEA) method. The hub genes coexpressed in multiple tissues were then screened out using data sets of synovium, cartilage, chondrocyte, subchondral bone, and synovial fluid samples. Finally, transcriptional factors and coexpressed hub genes were validated via experiments. Results The turquoise module of GSE55235 was identified via WGCNA. Functional annotation analysis showed that “mineral absorption” and “FoxO signaling pathway” were mostly enriched in the module. JUN, EGR1, FOSB, and KLF4 acted as central nodes in protein-protein interaction network and transcription factors to connect several target genes. “Activated B cell,” “activated CD4T cell,” “eosinophil,” “neutrophil,” and “type 17 T helper cell” showed high immune infiltration, while FOSB, KLF6, and MYBL2 showed significant negative correlation with type 17 T helper cell. Conclusions Our results suggest that the expression level of apolipoprotein D (APOD) was correlated with OA. Furthermore, transcriptional regulatory-immune network was constructed, which may contribute to OA therapy.

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The Role of the Transcription Factor EGR1 in Cancer

Cited by 137 publications

References 92 publications

Transcriptional Regulation of GDF15 by EGR1 Promotes Head and Neck Cancer Progression through a Positive Feedback Loop

Transcriptional Regulation of GDF15 by EGR1 Promotes Head and Neck Cancer Progression through a Positive Feedback Loop

Anti-Oxidative and Immune Regulatory Responses of THP-1 and PBMC to Pulsed EMF Are Field-Strength Dependent

Apolipoprotein D as a Potential Biomarker and Construction of a Transcriptional Regulatory-Immune Network Associated with Osteoarthritis by Weighted Gene Coexpression Network Analysis

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