Inhibition of REST Suppresses Proliferation and Migration in Glioblastoma Cells

被引:31
|
作者
Zhang, Dianbao [1 ,2 ]
Li, Ying [1 ,2 ]
Wang, Rui [1 ,2 ]
Li, Yunna [3 ]
Shi, Ping [4 ]
Kan, Zhoumi [5 ]
Pang, Xining [1 ,2 ,6 ]
机构
[1] China Med Univ, Shenyang Key Lab Stem Cells & Regenerat Med, Dept Stem Cells & Regenerat Med, Key Lab Cell Biol,Minist Publ Hlth,Minist Educ, Shenyang 110122, Peoples R China
[2] China Med Univ, Key Lab Med Cell Biol, Minist Educ, Shenyang 110122, Peoples R China
[3] Shenyang Childrens Hosp, Pharmaceut Preparat Sect, Shenyang 110032, Peoples R China
[4] China Med Univ, Affiliated Hosp 1, Dept Gen Practice, Shenyang 110015, Peoples R China
[5] China Med Univ, Affiliated Hosp 1, Dept Pharm, Shenyang 110015, Peoples R China
[6] China Med Univ, Sci Expt Ctr, Shenyang 110122, Peoples R China
关键词
glioblastoma; REST; NRSF; proliferation; migration; EPIGENETIC REGULATION; MALIGNANT GLIOMAS; EXPRESSION; RADIATION;
D O I
10.3390/ijms17050664
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Glioblastoma (GBM) is the most common primary brain tumor, with poor prognosis and a lack of effective therapeutic options. The aberrant expression of transcription factor REST (repressor element 1-silencing transcription factor) had been reported in different kinds of tumors. However, the function of REST and its mechanisms in GBM remain elusive. Here, REST expression was inhibited by siRNA silencing in U-87 and U-251 GBM cells. Then CCK-8 assay showed significantly decreased cell proliferation, and the inhibition of migration was verified by scratch wound healing assay and transwell assay. Using cell cycle analysis and Annexin V/PI straining assay, G1 phase cell cycle arrest was found to be a reason for the suppression of cell proliferation and migration upon REST silencing, while apoptosis was not affected by REST silencing. Further, the detection of REST-downstream genes involved in cytostasis and migration inhibition demonstrated that CCND1 and CCNE1 were reduced; CDK5R1, BBC3, EGR1, SLC25A4, PDCD7, MAPK11, MAPK12, FADD and DAXX were enhanced, among which BBC3 and DAXX were direct targets of REST, as verified by ChIP (chromatin immunoprecipitation) and Western blotting. These data suggested that REST is a master regulator that maintains GBM cells proliferation and migration, partly through regulating cell cycle by repressing downstream genes, which might represent a potential target for GBM therapy.
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页数:16
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