Effects of SIRT1 silencing on viability, invasion and metastasis of human glioma cell lines
Effects of SIRT1 silencing on viability, invasion and metastasis of human glioma cell lines
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DOI：
10.3892/ol.2019.10063
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发表时间：
2019-04-01
期刊：
影响因子：
2.9
通讯作者：
Wang, Xiaofang
中科院分区：
文献类型：
--
作者：
Li, Yu;Chen, Xin;Wang, Xiaofang
沉默信息调节因子1（SIRT 1）是沉默调节蛋白家族的成员之一，参与多种肿瘤的发生发展。先前的研究表明，SIRT 1在某些肿瘤中具有双重功能，作为启动子和抑制剂。然而，SIRT 1在胶质瘤细胞侵袭和转移中的作用及其相关信号通路尚不清楚。本研究的目的是确定SIRT 1对这些过程的影响，并对人脑胶质瘤和邻近组织中的上皮-间质转化（EMT），以及人脑胶质瘤细胞系U87和U251。采用逆转录-定量聚合酶链反应（RT-PCR）、免疫印迹法（Western blotting）和免疫组化法检测SIRT 1在组织中的表达。将U87和U251细胞系分为对照组和SIRT 1-小干扰RNA（siRNA）组。使用Cell Counting Kit-8细胞侵袭测定来评估SIRT 1沉默对细胞活力、侵袭和EMT的影响。结果表明SIRT 1在胶质瘤组织中的表达高于癌旁组织。此外，SIRT 1-siRNA显著抑制U87和U251细胞的活力和侵袭。此外，EMT分析显示，与对照组相比，SIRT 1-siRNA组中间充质标志物纤连蛋白和波形蛋白的表达水平显著降低。相反，与对照组相比，SIRT 1-siRNA组中上皮标志物上皮钙粘蛋白和β-连环蛋白的表达水平显著更高。总之，本研究的结果表明，SIRT 1与U87细胞的活力和侵袭性正相关，可能通过EMT。这些结果表明SIRT 1可能在胶质瘤的增殖和发展中起重要作用。
Silent information regulator 1 (SIRT1), a member of the sirtuin family, is involved in the development of various types of tumor. Previous studies have revealed that SIRT1 has dual functions, as a promoter and an inhibitor, in certain tumors. However, the role of SIRT1 in invasion and metastasis of glioma cells and its associated signaling pathway remain unclear. The aim of the present study was to determine the effects of SIRT1 on these processes and on the epithelial-mesenchymal transition (EMT) in human glioma and adjacent tissues, and in the human glioma cell lines U87 and U251. SIRT1 expression in tissues was investigated using the reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. The U87 and U251 cell lines were divided into control and SIRT1-small interfering RNA (siRNA) groups. The Cell Counting Kit-8, cell invasion assays were used to evaluate the effects of SIRT1 silencing on cell viability, invasion and EMT. Results indicated that SIRT1 was highly expressed in glioma tissues compared with in adjacent brain tissues. In addition, SIRT1-siRNA significantly inhibited the viability and invasion of U87 and U251 cells. Furthermore, EMT analysis revealed that the expression levels of the mesenchymal markers fibronectin and vimentin were significantly lower in the SIRT1-siRNA group compared with in the control group. Conversely, expression levels of the epithelial markers epithelial cadherin and beta-catenin were significantly higher in the SIRT1-siRNA group compared with in the control group. In conclusion, the results of the present study indicated that SIRT1 was positively associated with viability and invasion of U87 cells, potentially through EMT. These results suggested that SIRT1 may serve a crucial role in the proliferation and development of glioma.