Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China; School of Nursing, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Neurosci Lett. 2019 Jul 13;705:80-86. doi: 10.1016/j.neulet.2019.04.038. Epub 2019 Apr 18.
Glioma stem cells (GSC) were important for Glioblastoma (GBM) initiation and chemotherapy resistance. Centrosomal protein of 55 kDa (CEP55) was a biomarker for multiple cancers. However, roles and mechanism of CEP55 in glioma tumorigenesis and stemness maintains of stem like cells was still unclear. U251 cells which stable overexpression or downregulation of CEP55 was obtained by lentivirus mediated transduction. Roles and mechanism of CEP55 in stemness maintains of stem like cells and tumorigenesis was investigated. Our results implied that knockdown the expression of CEP55 inhibited the invasion and migration of U251 cells, while overexpression of CEP55 displayed opposite results. Moreover, overexpression of CEP55 promoted neurosphere formation of glioma stem-like cells, while CEP55 knockdown decreased the number and size of neurosphere. Mechanistically, overexpression of CEP55 enhanced the expression of Forkhead box protein M1 (FOXM1), Matrix metalloproteinases (MMPs) and activated the NF-κB pathway, while knockdown CEP55 displayed opposite results. In conclusion, our results indicated that CEP55 played an important role in promoting the invasion and migration of U251 cell and self-renewal of glioma stem like cells which might be a new therapeutic target for glioma.
神经胶质瘤干细胞（GSC）对于神经胶质瘤（GBM）的发生和化疗耐药至关重要。中心体 55kDa 蛋白（CEP55）是多种癌症的生物标志物。然而，CEP55 在神经胶质瘤发生和干细胞样细胞干性维持中的作用和机制仍不清楚。通过慢病毒介导的转导获得了稳定过表达或下调 CEP55 的 U251 细胞。研究了 CEP55 在干细胞样细胞干性维持和致瘤性中的作用和机制。我们的结果表明，敲低 CEP55 的表达抑制了 U251 细胞的侵袭和迁移，而过表达 CEP55 则显示出相反的结果。此外，过表达 CEP55 促进了神经球形成，而 CEP55 敲低则减少了神经球的数量和大小。机制上，过表达 CEP55 增强了叉头框蛋白 M1（FOXM1）、基质金属蛋白酶（MMPs）的表达并激活了 NF-κB 通路，而敲低 CEP55 则显示出相反的结果。总之，我们的结果表明，CEP55 在促进 U251 细胞的侵袭和迁移以及神经胶质瘤干细胞样细胞的自我更新中发挥了重要作用，这可能为神经胶质瘤提供了一个新的治疗靶点。
