ArticleBritish journal of cancer2015
Early Growth Response 3 regulates genes of inflammation and directly activates IL6 and IL8 expression in prostate cancer.
Article in British journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 81 citations in OpenAlex.
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- EGR3 reduces podocyte inflammatory damage in obesity related glomerulopathy by inhibiting the PRMT1Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Article
- IκBζ is an essential mediator of immunity to oropharyngeal candidiasis.Cell host & microbe · 2023Article
- Multi-Anticancer Activities of Phytoestrogens in Human Osteosarcoma.International journal of molecular sciences · 2023Review
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- Epigenome-Wide Association Studies of the Fractional Exhaled Nitric Oxide and Bronchodilator Drug Response in Moderate-to-Severe Pediatric Asthma.Biomedicines · 2023Article
- Intrafusal-fiber LRP4 for muscle spindle formation and maintenance in adult and aged animals.Nature communications · 2023Article
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- Identification of a neural development gene expression signature in colon cancer stem cells reveals a role foriScience · 2022Article
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- Multiple Effects of Resveratrol on Osteosarcoma Cell Lines.Pharmaceuticals (Basel, Switzerland) · 2022Article
- MYBL2 accelerates epithelial-mesenchymal transition and hepatoblastoma metastasis via the Smad/SNAI1 pathway.American journal of cancer research · 2022Article
- Interrogation of the microenvironmental landscape in spinal ependymomas reveals dual functions of tumor-associated macrophages.Nature communications · 2021Article
- XIST promotes apoptosis and the inflammatory response in CSE-stimulated cells via the miR-200c-3p/EGR3 axis.BMC pulmonary medicine · 2021Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTranscription factor EGR3 (Early Growth Response 3) is a little-studied member of the EGR family that is highly expressed in human prostate tumours compared with normal tissue. Its function in prostate cancer, however, is unknown.
methodsStable shRNA silencing was achieved in naturally overexpressing prostate cancer cells, followed by Affymetrix expression analysis. Fold changes of ⩾2 and ⩽-2 were considered valid and t-tests P-values of ⩽0.01 were considered statistically significant. Potential EGR3 target genes were validated by real-time qPCR, chromatin immunoprecipitation, and gain-of-function experiments. Promoter analysis confirmed the presence of consensus binding sites in the promoters of target genes.
resultsEarly Growth Response 3 regulates the expression of ∼330 genes, 35% of which are involved in immune responses and inflammatory processes, and 15% crosstalk with the NF-κB signalling pathway. In particular, EGR3 induces the expression of over 50 secreted cytokines, growth factors, and matrix remodelling factors. Two interleukins of great relevance to prostate cancer, IL6 and IL8, were further validated as EGR3 target genes: both promoters contain EGR consensus binding sites and are pulled down in intact cells by EGR3 chromatin immunoprecipitation. Silencing of EGR3 decreased IL6 and IL8 expression, whereas overexpression of EGR3 in nontransformed cells induced IL6 and IL8 expression.
conclusionsChronic inflammation plays a critical role in prostate cancer and elevated production of pro-inflammatory cytokines IL8 and IL6, in particular, contributes to disease progression and to the onset of castration resistance. It is shown for the first time that EGR3 is involved in the upregulation of both IL6 and IL8. Together with our previous observation that EGR3 is highly expressed in prostate tumours compared with normal tissue and strongly correlates with IL6 and IL8 expression in clinical samples, the present study suggests that EGR3 promotes excessive production of IL6 and IL8 observed during the progression of prostate cancer.
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