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. 2020 Oct;20(4):63.
doi: 10.3892/ol.2020.11924. Epub 2020 Jul 29.

Comprehensive analysis of a long non-coding RNA-associated competing endogenous RNA network in glioma

Jie Zhu  1 , Han Wang  2 , Yue-Qing Huang  3 , Wei Song  4 , Yi-Fan Li  5 , Wen-Jie Wang  6 , Zhi-Liang Ding  7
Affiliations

Comprehensive analysis of a long non-coding RNA-associated competing endogenous RNA network in glioma

Jie Zhu et al. Oncol Lett. 2020 Oct.

Abstract

Long non-coding RNAs (lncRNAs) can act as competing endogenous RNAs (ceRNAs), interacting with microRNAs (miRNAs) and playing an important role in tumor progression. However, the role of lncRNA-mediated ceRNAs in glioma remains largely unknown. The present study aimed to identify novel lncRNAs and their associated function in glioma. RNA sequencing and corresponding clinical data from patients with glioma were obtained from The Cancer Genome Atlas. A total of 598 glioma tissues and 5 normal brain tissues were analyzed in the present study. The differentially expressed (DE) lncRNAs, mRNAs and miRNAs were identified using R packages and were used to construct a ceRNA network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to investigate the biological functions of the DEmRNAs. Kaplan-Meier curve analysis was performed to investigate the association between DElncRNA expression and patient outcome. A total of 752 DElncRNAs, 2,079 DEmRNAs and 113 DEmiRNAs were identified between glioma and normal tissues. A lncRNA-miRNA-mRNA ceRNA network consisting of 61 lncRNAs, 12 miRNAs and 92 mRNAs was constructed. Survival analysis indicated that 36 DElncRNAs, 72 DEmRNAs and 3 DEmiRNAs were associated with overall survival in patients with glioma. The present study identified novel lncRNAs associated with survival prognosis and may facilitate further investigation of lncRNA-mediated ceRNA regulatory mechanisms in glioma.

Keywords: competitive endogenous RNA; glioma; long non-coding RNA; survival analysis.

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Figures

Figure 1.
Figure 1.
Volcano plot of differentially expressed (A) mRNAs, (B) lncRNAs and (C) miRNAs. Red dots represent upregulated RNAs and green dots represent downregulated RNAs with statistical significance. P<0.01 indicated a statistically significant difference. lncRNAs, long non-coding RNAs; miRNAs, microRNAs; FDR, false discovery rate; FC, fold change.
Figure 2.
Figure 2.
Heatmap of differentially expressed mRNAs between glioma and non-tumor tissues.
Figure 3.
Figure 3.
Heatmap of differentially expressed long non-coding RNAs between glioma and non-tumor tissues.
Figure 4.
Figure 4.
Heatmap of differentially expressed microRNAs between glioma and non-tumor tissues.
Figure 5.
Figure 5.
Venn diagram of differentially expressed mRNAs involved in the competing endogenous RNA network. A total of 92 DEmRNAs were included in the ceRNA network. Red, differentially expressed mRNAs; blue, target genes of miRNAs included in miRTarBase, miRDB and TargetScan databases; intersection, DEmRNAs.
Figure 6.
Figure 6.
Competing endogenous RNA network of lncRNA-miRNA-mRNA in glioma. lncRNA, long non-coding RNA; miRNA, microRNA.
Figure 7.
Figure 7.
Network of top-10 based on closeness in the competing endogenous RNA network. The network consisted of 6 miRNAs, including hsa-mir-93, hsa-mir-424, hsa-mir-497, hsa-mir-195, hsa-mir-182 and hsa-mir-96 and 4 lncRNAs, FAM87A, family with sequence similarity 87 member A; DLEU1, deleted in lymphocytic leukemia 1; LY86-AS1, lymphocyte antigen 86 antisense RNA 1; AC092171.1, non-protein coding RNA. Boxes with rounded edges, miRNAs; boxes with hexagon edges, lncRNAs.
Figure 8.
Figure 8.
Enriched GO biological process terms of differentially expressed mRNAs involved in the competing endogenous RNA network. GO, Gene Ontology; FC, fold change.
Figure 9.
Figure 9.
Top-9 enriched Kyoto Encyclopedia of Genes and Genomes pathway of differentially expressed mRNAs involved in the competing endogenous RNA network.
Figure 10.
Figure 10.
Kaplan-Meier survival curves of 6 differentially expressed long non-coding RNAs associated with overall survival in glioma. Overall survival curves of (A) DLEU1, (B) DBH-AS1, (C) HAS2-AS1, (D) LINC00320, (E) MEG8 and (F) MIR600HG. DLEU1, deleted in lymphocytic leukemia 1; DBH-AS1, dopamine β-hydroxylase antisense RNA1; HAS2-AS1, hyaluronan synthase 2 antisense RNA 1; LINC00320, long intergenic non-protein coding RNA 320; MEG8, maternally expressed 8.
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