Knockdown of STAT3 expression by RNAi suppresses growth and induces apoptosis and differentiation in glioblastoma stem cells
Knockdown of STAT3 expression by RNAi suppresses growth and induces apoptosis and differentiation in glioblastoma stem cells
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RNAi 敲低 STAT3 表达可抑制胶质母细胞瘤干细胞的生长并诱导其凋亡和分化
DOI：
10.3892/ijo_00000658
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发表时间：
2010-07-01
影响因子：
5.2
通讯作者：
Wang, Dong-Lin
中科院分区：
文献类型：
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作者：
Li, Guang-Hui;Wei, Hong;Wang, Dong-Lin
胶质母细胞瘤是人类原发性神经系统肿瘤中的一种高致死性脑肿瘤。以前的研究表明，胶质母细胞瘤干细胞能够启动和改革原来的癌症。本研究发现，人胶质母细胞瘤干细胞（GSCs）中存在着一种重要的信号转导因子和癌蛋白STAT 3的表达和激活。STAT 3在胚胎干细胞和几种癌症类型的增殖、凋亡和分化中起关键作用。为了研究STAT 3对人GSCs的影响，采用慢病毒介导的RNAi技术抑制STAT 3的表达和激活。我们证明，STAT 3的siRNA显著抑制STAT 3的表达和激活，并导致GSC中细胞生长的抑制。STAT 3基因敲低可诱导人原代GSCs凋亡，并显著降低Bcl-2和cyclin-D的表达，而BAX和caspase-3的表达无显著性差异。STAT 3表达的抑制不仅与CD 133（+）细胞比例的降低和GFAP和MBP表达的增加有关，而且与人原代GSC中引发肿瘤的能力的降低有关。总之，这些研究表明，STAT 3是人GSC在调节GSC生长、凋亡、分化和致瘤潜力中的重要靶点。
Glioblastoma is a highly lethal brain tumor of the human primary nervous system tumors. Previous studies demonstrated that glioblastoma stem cells were able to initiate and reform the original cancer. in this study, we found that there were expression and activation of STAT3, a key signal transduction factor and oncoprotein, in human glioblastoma stem cells (GSCs). STAT3 plays a key role in proliferation, apoptosis and differentiation in embryonic stem cells and several cancer types. To investigate the effects of STAT3 on human GSCs, the expression and activation of STAT3 were suppressed by RNAi mediated with lentivirus. We demonstrated that siRNA of STAT3 significantly suppressed STAT3 expression and activation and resulted in inhibition of cell growth in GSCs. Knockdown of STAT3 induces apoptosis and reduces significantly expression of Bcl-2 and cyclin-D in human primary GSCs, whereas no significance was achieved in BAX and caspase-3 expression. inhibition of STAT3 expression is associated not only with decreasing of CD133(+) cell proportion and increasing of GFAP and MBP exression, but also with decrease of the capacity to initiate a tumor in human primary GSCs. Together, these studies suggest that STAT3 is an important target for human GSCs in regulation of GSCs growth, apoptosis, differentiation and tumorigenic potential.