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尤因肉瘤异常甲基化差异表达基因及潜在药物的鉴定

Identification of aberrantly methylated-differentially expressed genes and potential agents for Ewing sarcoma.

作者信息

Li Guowang, Zhou Xuan, Tian Lijun, Meng Gedong, Li Bo, Yu Hao, Li Yongjin, Huo Zhenxin, Du Lilong, Ma Xinlong, Xu Baoshan

机构信息

Graduate School of Tianjin Medical University, Tianjin, China.

Department of Minimally Invasive Spine Surgery, Tianjin Hospital, Tianjin, China.

出版信息

Ann Transl Med. 2021 Oct;9(20):1557. doi: 10.21037/atm-21-4972.

DOI:10.21037/atm-21-4972
PMID:34790763
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8576650/
Abstract

BACKGROUND

Human DNA methylation is a common epigenetic regulatory mechanism, and it plays a critical role in various diseases. However, the potential role of DNA methylation in Ewing sarcoma (ES) is not clear. This study aimed to explore the regulatory roles of DNA methylation in ES.

METHODS

The microarray data of gene expression and methylation were downloaded from the Gene Expression Omnibus (GEO) database, and analyzed via GEO2R. Venn analysis was then applied to identify aberrantly methylated-differentially expressed genes (DEGs). Subsequently, function and pathway enrichment analysis was conducted, a protein-protein interaction (PPI) network was constructed, and hub genes were determined. Besides, a connectivity map (CMap) analysis was performed to screen bioactive compounds for ES treatment.

RESULTS

A total of 135 hypomethylated high expression genes and 523 hypermethylated low expression genes were identified. The hypomethylated high expression genes were enriched in signal transduction and the apoptosis process. Meanwhile, hypermethylated low expression genes were related to DNA replication and transcription regulation. The PPI network analysis indicated , , and might serve as diagnostic and therapeutic targets of ES. Furthermore, CMap analysis revealed 6 chemicals as potential options for ES treatment.

CONCLUSIONS

The introduction of DNA methylation characteristics over DEGs is helpful to understand the pathogenesis of ES. The identified hub aberrantly methylated DEGs and chemicals might provide some novel insights on ES treatment.

摘要

背景

人类DNA甲基化是一种常见的表观遗传调控机制，在多种疾病中发挥关键作用。然而，DNA甲基化在尤因肉瘤（ES）中的潜在作用尚不清楚。本研究旨在探讨DNA甲基化在ES中的调控作用。

方法

从基因表达综合数据库（GEO）下载基因表达和甲基化的微阵列数据，并通过GEO2R进行分析。然后应用韦恩分析来鉴定异常甲基化差异表达基因（DEGs）。随后进行功能和通路富集分析，构建蛋白质-蛋白质相互作用（PPI）网络，并确定枢纽基因。此外，进行连通性图谱（CMap）分析以筛选用于ES治疗的生物活性化合物。

结果

共鉴定出135个低甲基化高表达基因和523个高甲基化低表达基因。低甲基化高表达基因富集于信号转导和凋亡过程。同时，高甲基化低表达基因与DNA复制和转录调控有关。PPI网络分析表明， 、 和 可能作为ES的诊断和治疗靶点。此外，CMap分析揭示了6种化学物质作为ES治疗的潜在选择。

结论

引入DEGs的DNA甲基化特征有助于理解ES的发病机制。鉴定出的枢纽异常甲基化DEGs和化学物质可能为ES治疗提供一些新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/241b/8576650/48cd164347cf/atm-09-20-1557-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/241b/8576650/31b22bfc44bf/atm-09-20-1557-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/241b/8576650/8c724ca95d94/atm-09-20-1557-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/241b/8576650/a2c7210ac5fa/atm-09-20-1557-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/241b/8576650/558ed149eca2/atm-09-20-1557-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/241b/8576650/f6f845959c51/atm-09-20-1557-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/241b/8576650/48cd164347cf/atm-09-20-1557-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/241b/8576650/31b22bfc44bf/atm-09-20-1557-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/241b/8576650/8c724ca95d94/atm-09-20-1557-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/241b/8576650/a2c7210ac5fa/atm-09-20-1557-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/241b/8576650/558ed149eca2/atm-09-20-1557-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/241b/8576650/f6f845959c51/atm-09-20-1557-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/241b/8576650/48cd164347cf/atm-09-20-1557-f6.jpg

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