Musashi1 modulates glioma cell growth caused due to the regulation of cell cycle

Musashi1 （MSI1）是一种rna结合蛋白，在神经系统发育和干细胞自我更新中起着至关重要的作用。在这里，我们研究了它在胶质瘤进展中的作用。在胶质母细胞瘤和髓母细胞瘤细胞中，基于rnai的msi1敲低（KD）导致第30天集落形成细胞数量显著减少（集落大小减少66%），表明MSI1-KD对肿瘤细胞生长有抑制作用。免疫细胞化学染色MSI1-KD胶质母细胞瘤细胞提示这些细胞异位表达中期标志物。荧光细胞分选检测到G2/M期MSI1-KD细胞数量增加2.2倍，进一步证实MSI1-KD处理诱导有丝分裂和细胞存活缺陷，但未改变活化caspase-3的表达。我们进一步发现，MSI1-KD胶质母细胞瘤细胞异种移植物比对照组（33.6±3.6天，P<0.01）的生物发光成像系统（BLI）测量的肿瘤大小减少96.6%，生存时间（49.3±6.1天）更长。综上所述，这些发现和基因分析表明，胶质瘤细胞中MSI1-KD通过积累cyclin B，降低Notch信号通路活性，同时m-Numb上调，从而导致细胞周期延长，从而导致胶质瘤细胞存活率降低。

The expression of Musashi1 (MSI1), an RNA-binding protein that plays a crucial role in nervous system development and stem cell self-renewal. Here, we examined its role in the progression of glioma. The RNAi-based MSI1-knock down (KD) in glioblastoma and medulloblastoma cells resulted in a significantly lower number of colony forming cells on day 30 (66% reduction in colony size), indicative of the inhibitory effect of MSI1-KD on tumor cell growth. Immunocytochemical staining of MSI1-KD glioblastoma cells suggested that these cells ectopically express markers of Meta-phase. A 2.2 -fold increased number of MSI1-KD cells in the G2/M phase, as detected by fluorescence cell sorting, further confirmed the induction of mitosis and defect of cell survival upon MSI1-KD treatment, although it did not alter the expression of, activated caspase-3. We further showed that the xenografts of MSI1-KD glioblastoma cells had a 96.6% reduction of tumor size measured by bioluminescence imaging system(BLI) and longer survival (49.3±6.1 days) than the control group (33.6±3.6 days ; P<0.01). Taken together, these findings and gene analysis suggest that in MSI1-KD in glioma cells results in the prolongation of the cell cycle by accumulating cyclin B and reduced activity of Notch signal pathway accompanying with up-regulation of m-Numb, which could cause the decrease of survival of glioma cells..