含溴结构域4转录激活的Deltex E3泛素连接酶2促进胶质瘤进展并预示不良预后。

Bromodomain containing 4 transcriptionally activated Deltex E3 ubiquitin ligase 2 contributes to glioma progression and predicts an unfavorable prognosis.

作者信息

Wu Shizhong, Shen Shang-Hang, Lu Feng, Zheng Pengfeng, Lin Kun, Liao Jingwei, Jiang Xiaohang, Zeng Guangming, Wei De

机构信息

Department of Neurosurgery, Fujian Provincial Hospital South Branch, Fuzhou, China.

Department of Neurosurgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.

出版信息

Ann Transl Med. 2022 Mar;10(6):313. doi: 10.21037/atm-22-555.

DOI:10.21037/atm-22-555

PMID:35434025

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9011215/

Abstract

BACKGROUND

Glioblastoma multiforme (GBM) is the most common type of glioma, and the most aggressive brain malignancy in adults. This study sought to identify novel survival-status related markers, and examine their function in glioma.

METHODS

The gene expression, survival heatmaps, and Kaplan-Meier survival plots of the genes were analyzed by using gene expression profiling interactive analysis (GEPIA) dataset, Linked Omics. The single-cell data analysis and tumor immune infiltration analysis was conducted by Tumor Immune Estimation Resource (TIMER) dataset. DBTRG and U251 cells with silenced Deltex E3 ubiquitin ligase 2 () expression were constructed and used for Cell Counting Kit 8 (CCK-8), and wound healing assay in vitro. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis was used to explore the histone activation marks and transcription factors promoter. Dual-luciferase assays were carried out to detect the luciferase activities of bromodomain containing 4 () binding to .

RESULTS

We first conducted a survival-status analysis to identify survival status-related genes in The Cancer Genome Atlas GBM and low-grade glioma data sets. A subsequent analysis identified 3 novel prognostic biomarkers; that is, , cytochrome P450 oxidoreductase, and Williams-Beuren syndrome chromosomal region 16 protein. In the validation Chinese Glioma Genome Atlas data sets, showed the best performance, and was examined in a further analysis. Next, 3 short-hairpin ribonucleic acids were designed to silence expression, and CCK-8 and wound-healing assays were applied to study the function of . We found that -silenced glioma cells exhibited a significant decrease in their growth and migration capabilities. Finally, the molecular basis for increased in glioma was investigated via ChIP-Seq analysis and luciferase assays. The analysis revealed that was transcriptionally activated by .

CONCLUSIONS

In conclusion, transcriptionally activates , contributes to glioma progression, predicts an unfavorable prognosis, and could provide new options for glioma prognosis prediction and treatment.

摘要

背景

多形性胶质母细胞瘤（GBM）是最常见的胶质瘤类型，也是成人中最具侵袭性的脑恶性肿瘤。本研究旨在鉴定与生存状态相关的新标志物，并研究它们在胶质瘤中的功能。

方法

使用基因表达谱交互分析（GEPIA）数据集、Linked Omics分析基因的基因表达、生存热图和基因的Kaplan-Meier生存曲线。通过肿瘤免疫估计资源（TIMER）数据集进行单细胞数据分析和肿瘤免疫浸润分析。构建了沉默Deltex E3泛素连接酶2（）表达的DBTRG和U251细胞，并用于体外细胞计数试剂盒8（CCK-8）和伤口愈合试验。染色质免疫沉淀测序（ChIP-seq）分析用于探索组蛋白激活标记和转录因子启动子。进行双荧光素酶测定以检测含溴结构域4（）与结合的荧光素酶活性。

结果

我们首先进行了生存状态分析，以鉴定癌症基因组图谱GBM和低级别胶质瘤数据集中与生存状态相关的基因。随后的分析鉴定出3种新的预后生物标志物，即、细胞色素P450氧化还原酶和威廉姆斯-博伦综合征染色体区域16蛋白。在验证性的中国胶质瘤基因组图谱数据集中，表现最佳，并在进一步分析中进行了检测。接下来，设计了3种短发夹核糖核酸以沉默表达，并应用CCK-8和伤口愈合试验研究的功能。我们发现沉默的胶质瘤细胞的生长和迁移能力显著降低。最后，通过ChIP-Seq分析和荧光素酶测定研究了胶质瘤中升高的分子基础。分析表明被转录激活。