Knockdown of SALL4 expression using RNA interference induces cell cycle arrest, enhances early apoptosis, inhibits invasion and increases chemosensitivity to temozolomide in U251 glioma cells

被引:13
作者
Zhang, Lei [1 ]
Yan, Yong [1 ]
Jiang, Ying [1 ]
Qian, Jun [1 ]
Jiang, Lei [1 ]
Hu, Guohan [1 ]
Lu, Yicheng [1 ]
Luo, Chun [1 ]
机构
[1] Second Mil Med Univ, Changzheng Hosp, Dept Neurosurg, 415 Fengyang Rd, Shanghai 200003, Peoples R China
基金
上海市自然科学基金; 中国国家自然科学基金;
关键词
glioblastoma; U251; spalt-like transcription factor 4; short interfering RNA; STEM-CELL; CANCER; IDENTIFICATION; RESISTANCE; MGMT;
D O I
10.3892/ol.2017.6722
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Spalt-like transcription factor 4 (SALL4) is essential for the maintenance of the self-renewal and pluripotent properties in embryonic stem cells. Although the detailed mechanism remains unclear, dysregulation of SALL4 has been detected in various malignancies. Previously, the authors' of the present study reported that the expression level of SALL4 was associated with the poor prognosis of glioblastoma multiforme (GBM). The present study aimed to investigate the function of SALL4 in U251 human glioblastoma cells, including apoptosis and invasion inhibition. It was revealed that knockdown of SALL4 expression through RNA interference induced cell cycle arrest, enhanced early apoptosis and significantly inhibited invasion. Furthermore, downregulation of SALL4 was associated with a significantly lower expression level of the core transcription factors, including POU class 5 homeobox 1, SRY-box 2 and Nanog homeobox. In addition, inhibition of SALL4 significantly reduced the concentration of chemotherapeutic agent temozolomide required to inhibit cell growth by 50%, which decreased from 113.66 +/- 23.07 and 114.93 +/- 20.91 mu g/ml to 68.34 +/- 3.52 and 67.44 +/- 4.71 mu g/ml in two independent short interfering RNA transfected groups. These results indicate that SALL4 serves an important role in the GBM pathophysiology and targeting SALL4 may be a potential approach to the treatment of GBM.
引用
收藏
页码:4263 / 4269
页数:7
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