Nucleostemin promotes the proliferation of human glioma via Wnt/-Catenin pathway
Nucleostemin promotes the proliferation of human glioma via Wnt/-Catenin pathway
复制标题
Nucleostemin 通过 Wnt/-Catenin 通路促进人胶质瘤增殖
DOI：
10.1111/neup.12265
复制
发表时间：
2016-06-01
期刊：
影响因子：
2.3
通讯作者：
Cui, Gang
中科院分区：
文献类型：
--
作者：
Bao, Zhen;Wang, Yunfeng;Cui, Gang
核仁干细胞蛋白（Nucleostemin）是核仁三磷酸鸟苷（GTP）结合蛋白3（GTP binding protein 3），属于MMR 1/HSR 1 GTP结合蛋白家族。核干细胞蛋白在多种肿瘤的自我更新、细胞周期调控、细胞凋亡和细胞增殖中发挥重要作用。然而，其在人脑胶质瘤中的表达及其潜在功能尚不清楚。在本研究中，我们证明了nucleostemin的上调与不良的5年生存率密切相关。在U251和U373 MG血清饥饿和再喂养模型中，我们观察到核干细胞蛋白和p-连环蛋白（p-Tyr 645）的表达增加，并伴有细胞增殖标志物（细胞周期蛋白D1和增殖细胞核抗原（PCNA））。采用nucleostemin耗竭模型，我们发现下调nucleostemin和p-连环蛋白。流式细胞仪分析证实细胞增殖减弱。此外，我们还检测到-Catenin向细胞核的转位受到了抑制，这意味着Wnt/-Catenin通路受到了抑制。总之，我们确定了核干蛋白的上调和人脑胶质瘤细胞增殖之间的正相关性，敲低核干蛋白通过减少-连环蛋白向细胞核的运输来减轻胶质瘤增殖。提示nucleostemin可能通过Wnt/-Catenin途径促进人脑胶质瘤的增殖。
Nucleostemin, nucleolar guanosine triphosphate (GTP)-binding protein 3, is a member of the MMR1/HSR1 GTP-binding protein family. The important roles of nucleostemin in self-renewal, cell cycle regulation, apoptosis, and cell proliferation of various cancer types as been shown. Nevertheless, its expression and potential functions in human glioma is still unclear. In the present study, we demonstrated that up-regulation of nucleostemin was tightly related to poor 5-year-survival ratios. In serum-starved and re-feeding models of U251 and U373MG, we observed the rising expression of nucleostemin and p--Catenin (p-Tyr645) were accompanied with cell proliferation markers (cyclin D1 and proliferating cell nuclear antigen (PCNA)). Employing nucleostemin-depletion models, we found down-regulated nucleostemin and p--Catenin. The flow cytometry analysis proved the weakened cell proliferation. Moreover, we detected the translocation of -Catenin into the nucleus was impaired, meaning the inhibition of the Wnt/-Catenin pathway. Taken together, we identified a positive correlation between up-regulation of nucleostemin and human glioma cell proliferation and that knocking-down nucleostemin alleviated glioma proliferation by reducing -Catenin transportation into the nucleus. All results suggested that nucleostemin might accelerate human glioma proliferation via the Wnt/-Catenin pathway.