Shen Yun, Ye Yan-Rong, Tang Zhao-Qi
Department of Pharmacy, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China; Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Pharmacy, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China; Xiamen Clinical Research Center for Cancer Therapy, Xiamen, China.
World Neurosurg. 2023 Apr;172:e267-e277. doi: 10.1016/j.wneu.2023.01.007. Epub 2023 Jan 6.
Inducing the differentiation of glioma cells into neuron-like cells may be an effective strategy to combat glioma. The histone deacetylase 1/RE-1 silencing transcription factor (HDAC1/REST) complex regulates the expression of multiple neuronal genes. In this study, we analyzed the presence and significance of this regulatory effect in glioma based on bioinformatics methods.
The Human Protein Atlas database was used to obtain immunohistochemical staining images. The Gene Expression Profiling Interactive Analysis and Chinese Glioma Genome Atlas databases were used to analyze the expression of HDAC1/REST and neuronal markers in glioma, their effects on survival, and the association between HDAC1/REST and the expression of neuronal markers and stem cell markers. The differentially expressed genes between the high and low HDAC1/REST groups were explored. The Database for Annotation, Visualization and Integrated Discovery database was used for gene ontology and kyoto encyclopedia of genes and genomes pathway enrichment analysis.
The results showed that the expression of HDAC1 and REST increased with the grade of glioma, while the expression of neuronal markers decreased with the grade of glioma. High expression of HDAC1/REST and low expression of neuronal markers were associated with poor prognosis. HDAC1/REST expression was negatively correlated with the expression of neuronal markers, and positively correlated with the expression of neural stem cell markers. The genes up-regulated in the high HDAC1/REST group were mainly related to extracellular matrix and inflammation, and the down-regulated genes were mainly related to synapsis.
This study suggested that HDAC1/REST may be involved in maintaining the malignant phenotype of glioma cells and the stem cell status of glioma stem cells by inhibiting the expression of neuronal markers, which promote the progression of glioma.
诱导胶质瘤细胞分化为神经元样细胞可能是对抗胶质瘤的一种有效策略。组蛋白去乙酰化酶1/RE-1沉默转录因子（HDAC1/REST）复合物调节多种神经元基因的表达。在本研究中，我们基于生物信息学方法分析了这种调节作用在胶质瘤中的存在情况及意义。
使用人类蛋白质图谱数据库获取免疫组化染色图像。利用基因表达谱交互式分析数据库和中国胶质瘤基因组图谱数据库分析HDAC1/REST和神经元标志物在胶质瘤中的表达、它们对生存的影响以及HDAC1/REST与神经元标志物和干细胞标志物表达之间的关联。探索HDAC1/REST高表达组和低表达组之间的差异表达基因。使用注释、可视化和综合发现数据库进行基因本体论和京都基因与基因组百科全书通路富集分析。
结果显示，HDAC1和REST的表达随胶质瘤分级增加而升高，而神经元标志物的表达随胶质瘤分级降低。HDAC1/REST高表达和神经元标志物低表达与预后不良相关。HDAC1/REST表达与神经元标志物表达呈负相关，与神经干细胞标志物表达呈正相关。HDAC1/REST高表达组中上调的基因主要与细胞外基质和炎症相关，下调的基因主要与突触相关。
本研究表明，HDAC1/REST可能通过抑制神经元标志物的表达参与维持胶质瘤细胞的恶性表型和胶质瘤干细胞的干细胞状态，从而促进胶质瘤的进展。
