LncRNA-mediated ceRNA regulation varies among different molecular subtypes in glioblastoma.

Glioblastoma (GBM) is a malignant brain tumor associated with high mortality. Long non-coding RNAs (lncRNAs) are increasingly being recognized as its modulators. However, it remains mostly unexplored how lncRNAs are mediated by dNA methylation in GBM. The present study integrated multi-omics data to analyze the epigenetic dysregulation of lncRNAs in GBM. Widely aberrant methylation in the lncRNA promoters was observed, and the lncRNA promoters exhibited a more hypomethylated pattern in GBM. By combining transcriptional datasets, it was possible identify the lncRNAs whose transcriptional changes might be associated with the aberrant promoter methylation. Then, a methylation-mediated lncRNA regulatory network and functional enrichment analysis of aberrantly methylated lncRNAs showed that lncRNAs with different methylation patterns were involved in diverse GBM progression-related biological functions and pathways. Specifically, four lncRNAs whose increased expression may be regulated by the corresponding promoter hypomethylation were evaluated to have an excellent diagnostic effect and clinical prognostic value. Finally, through the construction of drug-target association networks, the present study identified potential therapeutic targets and small-molecule drugs for GBM treatment. The present study provides novel insights for understanding the regulation of lncRNAs by dNA methylation and developing cancer biomarkers in GBM.

Background Glioblastoma 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. Results We 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. Conclusions Our 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.