Expression of REST4 in human gliomas in vivo and influence of pioglitazone on REST in vitro

Ren, Huan; Gao, Zhangfeng; Wu, Na-Yi Yuan; Le, Zeng; Tang, Xiaozhi; Chen, Xiaoping; Liu, Zhao‐Qian; Zhang, Wei; Wang, Liansheng; Li, Zhi

doi:10.1016/j.bbrc.2015.05.058

Cited by 9 publications

(15 citation statements)

References 39 publications

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“…REST targets include a large number of genes and accumulated studies revealed that REST plays diverse roles in multiple cellular processes [ 6 ], it was originally discovered to repress neuron-specific genes in non-neuronal tissues and neural progenitors, and it was implicated as a tumor suppressor in breast cancer, colorectal cancer and small cell lung cancer, and as an oncogene in neuroblastomas, medulloblastomas and pheochromocytomas [ 7 , 8 ]. In GBM, previous studies showed enhanced REST protein levels in patient-derived specimens and tumorigenic-competent GBM cells [ 9 ], and inhibition of REST in GBM isolated cancer stem cells and subsequent implantation of these cells into mice resulted in tumors that were significantly less invasive, highly apoptotic and slower growing [ 10 , 11 , 12 ], partly through regulating tumor suppressor microRNA miR-124a and its downstream targets [ 13 ]. However, the detailed function of REST and its mechanisms in GBM are not very clear.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of REST Suppresses Proliferation and Migration in Glioblastoma Cells

Zhang

Wang

et al. 2016

IJMS

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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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Section: Introductionmentioning

confidence: 99%

Inhibition of REST Suppresses Proliferation and Migration in Glioblastoma Cells

Zhang

Wang

et al. 2016

IJMS

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“…Regardless of age, the expression of REST may also be upregulated when neural cells become malignant (8,9). In addition, a previous study identified a positive correlation between the expression of REST and the malignant degree of glioma (10).…”

Section: Repressor Element Silencing Transcription Factormentioning

confidence: 93%

“…Taken together, these data suggested that REST may promote glioma development and is elevated in glioma compared with adjacent normal tissues. Furthermore, the mRNA expression levels of REST were significantly increased in grade III-IV glioma compared with in grade I-II glioma (10), thus suggesting that the expression of REST is positively correlated with the degree of glioma malignancy. However, low expression of REST was also detected in mouse neuroblastoma cell lines, such as NS20Y (6,21,22).…”

Section: Rest In Glioma: Poor Prognosismentioning

confidence: 96%

“…It has also been suggested that REST4 combines with RE-1/NRSE; however, the protein-DNA interaction is considerably weaker than that of REST, thus resulting in weakened transcriptional repression (40). Furthermore, a recent study indicated that human glioma tissues that expressed REST4 exhibited reduced REST mRNA expression compared with tissues that did not express REST4 (10). Based on these findings, the present review hypothesized that REST4 may combine with REST; therefore, REST4 may be considered a therapeutic marker that can inhibit the expression of REST, so as to prevent the proliferation of glioma cells and tumor growth.…”

Section: Regulation and Function Of Rest4mentioning

confidence: 99%

“…In addition to these aforementioned factors, pioglitazone, an antidiabetic drug, has also been reported to affect REST expression in glioma. When U87 cells were treated with 50 and 100 µM pioglitazone, the relative expression levels of REST were significantly decreased and cell growth was inhibited (10). As a result, pioglitazone may be a potential treatment for glioma with high REST expression.…”

Section: Regulation Of Rest Expression In Gliomamentioning

confidence: 99%

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Molecular mechanisms and potential prognostic effects of REST and REST4 in glioma

Wang

Tang

et al. 2017

Molecular Medicine Reports

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Glioma refers to a tumor of the brain and central nervous system, which is characterized by high incidence, high mortality and high recurrence rate. Although the association between glioma and the repressor element silencing transcription factor (REST) has been reported by numerous studies, the complicated regulatory mechanisms underlying REST remain unknown. REST is a transcriptional repressor that undergoes alternative splicing to produce splicing variants when transcribed. Previous studies have demonstrated that alternative splicing may serve a role in the outcome of glioma. The present review discussed the mutual relationship among REST, REST4 and glioma. It was concluded that increased REST expression in glioma may be associated with poor prognosis; and REST4, an AS variant of REST, also functions to regulate glioma by suppressing REST. In addition, the present review discussed the regulation of REST and its target genes in glioma, and identified factors that induce REST alternative splicing, particularly in glioma. These findings suggest that REST may be considered a prognostic factor, which can be predictive of patient outcome.

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