组蛋白去乙酰化酶 SIRT6 通过下调 NOTCH3 表达抑制神经胶质瘤细胞生长。
Histone deacetylase SIRT6 inhibits glioma cell growth through down-regulating NOTCH3 expression.
机构信息
Department of Neurosurgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
出版信息
Acta Biochim Biophys Sin (Shanghai). 2018 Apr 1;50(4):417-424. doi: 10.1093/abbs/gmy019.
Gliomas are the most common brain tumors of the central nervous system. In this study, we investigated the molecular mechanisms and biological function of SIRT6 in human gliomas. The expression levels of SIRT6 in glioma tissues and cells were analyzed by qRT-PCR and western blot analysis. CCK8 and clonogenicity assays were performed to detect the cell proliferation. Furthermore, the migration and invasion of glioma cells were examined by transwell assays. It was found that the expression of SIRT6 was significantly lower in human glioma tissues or cell lines compared with the normal brain tissue or NHA. Up-regulated SIRT6 significantly decreased cell proliferation, migration and invasion of U87 and U251 cells. By contrast, knockdown of SIRT6 dramatically increased cell proliferation, migration and invasion of U87 and U251 cells. Moreover, over expression of NOTCH3 significantly increased the cell proliferation, migration, and invasion of U87 and U251 cells. However, these effects were abolished after overexpression of SIRT6. These results suggest that SIRT6 may suppress cell proliferation, migration, and invasion via inhibition of the NOTCH3 signaling pathway in glioma.
神经胶质瘤是中枢神经系统最常见的脑肿瘤。在这项研究中，我们研究了 SIRT6 在人神经胶质瘤中的分子机制和生物学功能。通过 qRT-PCR 和 Western blot 分析分析了 SIRT6 在神经胶质瘤组织和细胞中的表达水平。通过 CCK8 和集落形成实验检测细胞增殖。此外，通过 Transwell 实验检测了神经胶质瘤细胞的迁移和侵袭。结果发现，与正常脑组织或 NHA 相比，SIRT6 在人神经胶质瘤组织或细胞系中的表达明显降低。上调 SIRT6 可显著降低 U87 和 U251 细胞的增殖、迁移和侵袭。相比之下，SIRT6 的敲低显著增加了 U87 和 U251 细胞的增殖、迁移和侵袭。此外，NOTCH3 的过表达显著增加了 U87 和 U251 细胞的增殖、迁移和侵袭。然而，过表达 SIRT6 后，这些作用被消除。这些结果表明，SIRT6 可能通过抑制 NOTCH3 信号通路抑制神经胶质瘤细胞的增殖、迁移和侵袭。
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