High expression of immunity-related GTPase family M protein in glioma promotes cell proliferation and autophagy protein expression

Abstract

Glioma is the commonest malignant tumor in the central nervous system (CNS), characterized by rapid growth. However, the molecular mechanism underlying the growth remains unclear. Immunity-related GTPase family M protein (IRGM) participates in immune response to pathogen and tumorigenesis. Proliferation and autophagy are two crucial functions contributing to aggressive growth. Therefore, our aims were to probe whether IRGM regulates glioma proliferation and autophagy. In this study, we found that 47 glioma specimens had more IRGM expression than 11 non-cancerous brain tissues with immunohistochemistry. IRGM was also up-regulated in human glioma cell lines U87, U251 and A172 and so on compared with immortalized astrocytes. Importantly, overexpression of IRGM significantly increased the cell colonies formation, cell proliferation and Akt activation (Thr308 and Ser473 sites) than matched control. On another hand, all of IRGM, autophagy marker LC3II and autophagy adaptor p62 gradually increased after starvation 2 and 4 h. Furthermore, western blot and immunofluorescence results showed that knockdown of IRGM inhibited the formation of LC3-II and the expression of p62. Our data uncovered that IRGM acted in glioma proliferation and autophagy, providing a new target with dual roles for the future translation research.

Keywords: Autophagy; Glioma; Immunity-related GTPase family M protein; Proliferation.