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Integrative analysis of DNA methylation and gene expression profiles identifies MIR4435-2HG as an oncogenic lncRNA for glioma progression
- Li, Zhijin, Tan, Hua, Zhao, Weiling, Xu, Yungang, Zhang, Zhigang, Wang, Maode, Zhou, Xiaobo
- Gene 2019 pp. 144012
- DNA methylation, biogenesis, disease progression, epigenetics, gene expression, gene expression regulation, genes, glioma, microRNA, microarray technology, non-coding RNA, prognosis, sequence analysis, signal transduction, tumor necrosis factor-alpha
- Long noncoding RNAs (lncRNAs) have been shown to play an important role in tumor biogenesis and prognosis. The glioma is a grade classified cancer, however, we still lack the knowledge on their function during glioma progression. While previous studies have shown how lncRNAs regulate protein-coding gene epigenetically, it is still unclear how lncRNAs are regulated epigenetically. In this study, we firstly analyzed the RNA-seq data systematically across grades II, IV, and IV of glioma samples. We identified 60 lncRNAs that are significantly differentially expressed over disease progression (DElncRNA), including well-known PVT1, HOTAIR, H19 and rarely studied CARD8-AS, MIR4435-2HG. Secondly, by integrating HM450K methylation microarray data, we demonstrated that some of the lncRNAs are epigenetically regulated by methylation. Thirdly, we developed a DESeq2-GSEA-ceRNA-survival analysis strategy to investigate their functions. Particularly, MIR4435-2HG is highly expressed in high-grade glioma and may have an impact on EMT and TNFα signaling pathway by functioning as a miRNA sponge of miR-125a-5p and miR-125b-5p to increase the expression of CD44. Our results revealed the dynamic expression of lncRNAs in glioma progression and their epigenetic regulation mechanism.