REST, not REST4, is a risk factor associated with radiotherapy plus chemotherapy efficacy in glioma.

BACKGROUND/AIM: Repressor element silencing transcription factor (REST) is a transcription repressor, expressed in several malignancies. This study aims to evaluate the prognostic values of REST and its splicing variant REST4 in glioma, and investigate the potential correlation between REST and REST4. METHODS: REST and REST4 expression values were evaluated by qRT-PCR in 89 patients with gliomas and 10 with normal brain tissues. RESULTS: Upregulation of REST was related to higher World Health Organization (WHO) grade, larger tumor size, higher ki67, and higher p53 positive rate. After radiotherapy+temozolomide (RT+TMZ) treatment, low REST expression patients could get better therapeutic efficacy (P=0.031). The positive rate of REST4 expression was only 13.5% in glioma tissues, and REST4 expression was not associated with clinical characteristics and REST expression in this study. CONCLUSIONS: REST was a prognostic factor in glioma, while REST4 was not. REST expression can be a predictor in evaluating the survival outcome of gliomas patients treated with RT+TMZ after surgery.

Molecular mechanisms and potential prognostic effects of REST and REST4 in glioma (Review).

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.