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Snail and ZEB2 play an oncogenic role in pediatric and adult glioblastoma cells through the induction of epithelial mesenchymal transition like process
교모세포종에서 상피중간엽 이행을 통한 Snail 및 ZEB2의 종양형성역할에 관한 연구

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Authors
명재경
Advisor
박성혜
Major
의과대학 의학과
Issue Date
2015-02
Publisher
서울대학교 대학원
Keywords
Epithelial mesenchymal transition (EMT)Glioblastomasmall interfering RNA (siRNA)SnailZEB2
Description
학위논문 (박사)-- 서울대학교 대학원 : 의학과, 2015. 2. 박성혜.
Abstract
Background: The factors affecting adult and pediatric glioblastoma progression are of great clinical importance since dismal outcomes have been observed for glioblastoma patients. Here, we focused on Epithelial mesenchymal transition (EMT) related factors as a key molecular factor in determining clinical outcome. The Snail and ZEB2 genes are known to coordinate the regulation of tumor progression in diverse tumors through induction of EMT
however, its role in pediatric and adult glioblastoma is still uncertain. Therefore, we aimed to further define its role in vitro.
Methods and Results: The small interfering RNA (siRNA) technique was employed to knock down Snail and ZEB2 expression in pediatric glioblastoma (KNS42) and adult glioblastoma cell lines (U87, and U373). Specific inhibition of both Snail and ZEB2 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 adult and pediatric glioblastoma cells as well as increased the number of cells in the G1 phase (G1 phase arrest). Also, inhibition of ZEB2 significantly reduced invasion and migration of both pediatric and adult glioblastoma cells. Interestingly, in pediatric glioblastoma, but not in adult glioblastoma cells, silencing of ZEB2 reduced cell proliferation, cell viability, and changed cell cycle progression of tumor cells, but these findings were not evoked in adult glioblastoma cells. Immunehistochemical staining for Snail and ZEB2 showed no difference between pediatric glioblastoma and adult glioblastoma. However, comparing to the immunoreactions of normal astrocytes and low grade glial tumors, glioblastoma cells showed relatively strong Snail and ZEB2 expression pattern. Also, mRNA for ZEB2 was higher in adult and pediatric glioblastoma cells than normal tissues.
Conclusions: Knockdown of Snail suppressed the proliferation, viability, migration, and invasion of adult and pediatric glioblastoma cells as well as inhibited cell cycle progression by promoting EMT like process. Also, inhibition of ZEB2 significantly reduced invasion and migration of both pediatric and adult glioblastoma cells. However, in pediatric glioblastoma cells, but not in adult glioblastoma cells, silencing of ZEB2 reduced cell proliferation, cell viability, and cell cycle progression of tumor cells. Our study demonstrated that Snail and ZEB2 play an oncogenic role in pediatric and adult glioblastoma by promoting EMT like process. However, unlike Snail, ZEB2 was shown to act differently on the cell proliferation, cell viability and cell cycle progression of pediatric and adult glioblastoma cells, which suggests that pediatric and adult glioblastoma may be different in certain biology and oncogenic process.
Language
Korean
URI
https://hdl.handle.net/10371/122042
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Theses (Ph.D. / Sc.D._의학과)
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