The regulatory pattern of target gene expression by aberrant enhancer methylation in glioblastoma

BMC Bioinformatics

Qiuhong Yu¹  Jianghuai Ji²  Rendong Wang³  Xiaoxiao Zhao³  Dongguo Li³  Shijia Wang³ 

[1]Department of Hyperbaric Oxygen, Beijing Tiantan Hospital, Capital Medical University, 119 Nansihuan Xi Lu, Fengtai District, 100070, Beijing, People’s Republic of China

[2]Department of Radiation Physics, Zhejiang Cancer Hospital, 310022, Hangzhou, People’s Republic of China

[3]Zhejiang Key Laboratory of Radiation Oncology, 310022, Hangzhou, People’s Republic of China

[4]School of Biomedical Engineering, Capital Medical University, 10 You An Men Wai, Xi Tou Tiao, 100069, Beijing, People’s Republic of China

[5]Beijing Key Laboratory of Fundamental Research on Biomechanics in Clinical, Capital Medical University, 100069, Beijing, People’s Republic of China

关键词: Glioblastoma multiforme;    Enhancer region;    DNA methylation;    Epigenetic regulation;    Biomarker;   

DOI  :  10.1186/s12859-021-04345-8

来源: Springer

【 摘 要 】

BackgroundGlioblastoma multiforme (GBM) is the most common and aggressive primary malignant brain tumor with grim prognosis. Aberrant DNA methylation is an epigenetic mechanism that promotes GBM carcinogenesis, while the function of DNA methylation at enhancer regions in GBM remains poorly described.ResultsWe integrated multi-omics data to identify differential methylation enhancer region (DMER)-genes and revealed global enhancer hypomethylation in GBM. In addition, a DMER-mediated target genes regulatory network and functional enrichment analysis of target genes that might be regulated by hypomethylation enhancer regions showed that aberrant enhancer regions could contribute to tumorigenesis and progression in GBM. Further, we identified 22 modules in which lncRNAs and mRNAs synergistically competed with each other. Finally, through the construction of drug-target association networks, our study identified potential small-molecule drugs for GBM treatment.ConclusionsOur study provides novel insights for understanding the regulation of aberrant enhancer region methylation and developing methylation-based biomarkers for the diagnosis and treatment of GBM.

【 授权许可】

CC BY