Myung Jae Kyung, Choi Seung Ah, Kim Seung-Ki, Wang Kyu-Chang, Park Sung-Hye
Department of Pathology, College of Medicine, Seoul National University Hospital Seoul, Korea.
Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital Seoul, Korea.
Int J Clin Exp Pathol. 2014 Apr 15;7(5):1977-87. eCollection 2014.
The factors affecting glioblastoma progression are of great clinical importance since dismal outcomes have been observed for glioblastoma patients. The Snail gene is known to coordinate the regulation of tumor progression in diverse tumors through induction of epithelial mesenchymal transition (EMT); however, its role in glioblastoma is still uncertain. Therefore, we aimed to further define its role in vitro.
The small interfering RNA (siRNA) technique was employed to knock down Snail expression in three glioblastoma cell lines (KNS42, U87, and U373). Specific inhibition of Snail expression increased E-cadherin expression but decreased vimentin expression in all cell lines. In addition, inhibition of the expression of Snail significantly reduced the proliferation, viability, invasion, and migration of glioblastoma cells as well as increased the number of cells in the G1 phase.
Knockdown of Snail suppresses the proliferation, viability, migration, and invasion of cells as well as inhibits cell cycle progression by promoting EMT induction. The findings suggest that expression of this gene facilitates glioblastoma progression. Therefore, these results indicate the clinical significance of Snail for use as a potential therapeutic target for glioblastoma.
由于胶质母细胞瘤患者的预后较差,影响胶质母细胞瘤进展的因素具有重要的临床意义。已知Snail基因通过诱导上皮-间质转化(EMT)来协调多种肿瘤中肿瘤进展的调控;然而,其在胶质母细胞瘤中的作用仍不确定。因此,我们旨在进一步确定其在体外的作用。
采用小干扰RNA(siRNA)技术敲低三种胶质母细胞瘤细胞系(KNS42、U87和U373)中Snail的表达。特异性抑制Snail表达可增加所有细胞系中E-钙黏蛋白的表达,但降低波形蛋白的表达。此外,抑制Snail的表达显著降低了胶质母细胞瘤细胞的增殖、活力、侵袭和迁移能力,并增加了处于G1期的细胞数量。
敲低Snail可抑制细胞的增殖、活力、迁移和侵袭,并通过促进EMT诱导来抑制细胞周期进程。这些发现表明该基因的表达促进了胶质母细胞瘤的进展。因此,这些结果表明Snail作为胶质母细胞瘤潜在治疗靶点的临床意义。