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

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

Oncology reports 2014 Nov

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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.

Citation

Jun Pan, Xiaoyong Zhao, Chunnan Lin, Hongchao Xu, Zhilin Yin, Tianzhu Liu, Shizhong Zhang. Immune responsive gene 1, a novel oncogene, increases the growth and tumorigenicity of glioma. Oncology reports. 2014 Nov;32(5):1957-66