GNL3对脑胶质瘤干细胞的调控研究

肿瘤干细胞是一小群特异的肿瘤细胞,被认为是肿瘤发生,耐药和复发的主要原因。GNL3(Guanine nucleotide-binding protein-like 3) 是MMR1/HSR1 GTP结合蛋白家族成员,在干细胞增殖中发挥重要作用。本实验室通过质谱筛选,发现GNL3蛋白在脑胶质瘤干细胞(Glioma stem cell,GSC)中特异性高表达。目前关于GNL3在脑胶质瘤干细胞中的功能及其作用机制未见文献报道。为了研究GNL3在GSC中的功能,我们利用慢病毒感染细胞体系,在GSC中应用3个不同的靶序列对GNL3基因的表达进行稳定干涉；利用Western Blot对GNL3的干涉效果进行检测。实验结果表明,在稳定敲低GNL3表达的GSC中,胶质瘤干细胞的细胞活力和肿瘤细胞球(Tumor sphere)的形成能力明显受到抑制,表明GNL3蛋白对GSC的增殖能力及自我更新能力具有重要调控,提示GNL3在胶质母细胞瘤的肿瘤发生过程中发挥一定作用。

The Roles of GNL3 on the Regulation of Glioma Stem Cell

Tumor stem cells are a small population of specific tumor cells,which are considered as the main source of tumorigenesis , drug resistance and recurrence. GNL3(Guanine nucleotide-binding protein-like 3), as a member of MMR1/HSR1 GTP binding protein family, plays an important role in stem cell proliferation. We found that GNL3 is specific highly expressed in the Glioma stem cell (GSC) by mass spectrometry screen. However,what functions of GNL3 in the GSC and the relative mechanism remain unknown. To investigate the specific function of GNL3 in the GSC, we used the lenti-virus particles infection system to stably knock down GNL3 with three different GNL3 target sequences. The knockdown efficiency of GNL3 shRNA was examined via Western Blot. Our results reveal that the cell viability and ability of tumor-sphere formation are inhibited in GNL3 stably knock-down GSCs compared with the control cells, suggesting that GNL3 is crucial for the cell proliferation and self-renewal. Moreover, this study suggested that GNL3 may contribute to the tumorigenesis of glioblastoma.