Investigation for the methylation-promoting element in response to carcinogenesis

本项目的目的是阐明癌变过程中选择性DNA甲基化的分子机制。我们检查了胶质瘤患者，发现IDH1突变胶质瘤中NRF2靶基因的表达水平显著低于IDH1 WT胶质瘤。当我们将IDH1突变体过表达到来自胶质瘤患者的细胞系之一T98细胞中时。IDH1突变细胞表现出NRF2靶基因的表达降低，NRF2在细胞核中的积累减少，NRF2基因的表达减少。本研究提示NRF 2基因在胶质瘤发生发展过程中可能存在表观遗传学沉默。

The goal of this project was to clarify the molecular mechanisms underlying the selective DNA methylation during carcinogenesis. We examined glioma patients and found that expression levels of NRF2 target genes in IDH1-mutated glioma are significantly lower than IDH1 WT glioma. When we overexpress IDH1 mutant into T98 cells, one of the cell lines derived from glioma patients. IDH1-mutant cells exhibited lower expression of NRF2 target genes, decreased accumulation of NRF2 in the nucleus, and reduced expression of NRF2 gene. This study has suggested a possibility that NRF2 gene might be epigenetically silenced during the development glioma.