Immune responsive gene 1, a novel oncogene, increases the growth and tumorigenicity of glioma

Pan,Jun; Zhao,Xiaoyong; Lin,Chunnan; Xu,Hongchao; Yin,Zhilin; Liu,Tianzhu; Zhang,Shizhong

doi:10.3892/or.2014.3474

Immune responsive gene 1, a novel oncogene, increases the growth and tumorigenicity of glioma

Authors:
- Jun Pan
- Xiaoyong Zhao
- Chunnan Lin
- Hongchao Xu
- Zhilin Yin
- Tianzhu Liu
- Shizhong Zhang
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Affiliations: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510000, P.R. China, Department of Neurosurgery, Huadu Hospital, Southern Medical University, Guangzhou, Guangdong 510000, P.R. China
Published online on: September 10, 2014 https://doi.org/10.3892/or.2014.3474
Pages: 1957-1966

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Abstract

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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