Immune responsive gene 1, a novel oncogene, increases the growth and tumorigenicity of glioma
Open accessAbstract
Immune responsive gene 1 (IRG1) is highly expressed in mammalian macrophages during inflammation. However, the role of IRG1 in tumorigenesis remains unclear. In the present study, we aimed to clarify the epigenetic regulation and biological functions of IRG1 in glioma. We found that the expression level of IRG1 influenced the WHO stage in 140 glioma patients. Overexpression of IRG1 increased the growth, invasion, and tumorigenesis in U251 and SHG-44 glioma cells both in vitro and in vivo. Suppression of IRG1 expression by si-IRG1 decreased the levels of cell cycle regulatory proteins, namely, E2F1, p21, CDK4, CDK6 and cyclin D1. Knockdown of IRG1 expression by RNA interference increased E-cadherin expression and decreased the amounts of snail and vimentin. Furthermore, the suppression of IRG1 expression inhibited the expression of NF-κB and STAT3, suggesting a role of IRG1 in regulating the genes associated with these factors and thereby contributing to a decrease in glioma cell proliferation, migration and invasion. Collectively, our findings revealed that IRG1 is a candidate oncogene that is amplified in glioma and is involved in novel mechanisms that influence glioma pathogenesis.
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Fumarate binds glutathione, forming succinic-glutathione, and depletes this antioxidant molecule leading to unscheduled oxidative stress.
“Later, it was also shown that fumarate binds glutathione (forming succinic-glutathione (succinicGSH)), and thereby depletes this antioxidant molecule leading to unscheduled oxidative stress83,84.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [84]
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- Authors
- PAN, J., ZHAO, X., LIN, C., XU, H., YIN, Z., LIU, T., & ZHANG, S.
- Affiliations
- Zhujiang Hospital (CN)
- Southern Medical University (CN)
- Venue
- Oncology Reports
- Publisher
- Spandidos Publications
- Published
- 2014-09-10
- Volume
- 32
- Issue
- 5
- Pages
- 1957-1966
- ISSN
- 1021-335X (ISSN-L)
- 1791-2431
- OpenAlex
- W2031650377
- Cited by
- 45
- References
- 26
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 4 · 2023: 10 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 2 · 2018: 3
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Oncology Reports (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81172416)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- IRG1, glioma, oncogenes, tumorigenicity, tumor invasion, cell proliferation, cell cycle regulation, E2F1, p21, CDK4, CDK6, cyclin D1, E-cadherin, snails, vimentin, epithelial-mesenchymal transition, NF-κB, STAT3, WHO grade, gene amplification
- MeSH terms
- Adult, Aged, Aged, 80 and over, Animals, Carboxy-Lyases, Female, Glioma, Humans, Male, Mice, Nude, Middle Aged, Neoplasm Transplantation, Oncogenes, Proteins, Signal Transduction, Cell Cycle Proteins, RNA, Small Interfering, Cell Line, Tumor, Mice
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