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Analyzing the interactions of mRNAs, miRNAs, lncRNAs and circRNAs to predict competing endogenous RNA networks in glioblastoma

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Abstract

Cross-talk between competitive endogenous RNAs (ceRNAs) may play a critical role in revealing potential mechanisms of tumor development and physiology. Glioblastoma is the most common type of malignant primary brain tumor, and the mechanisms of tumor genesis and development in glioblastoma are unclear. Here, to investigate the role of non-coding RNAs and the ceRNA network in glioblastoma, we performed paired-end RNA sequencing and microarray analyses to obtain the expression profiles of mRNAs, lncRNAs, circRNAs and miRNAs. We identified that the expression of 501 lncRNAs, 1999 mRNAs, 2038 circRNAs and 143 miRNAs were often altered between glioblastoma and matched normal brain tissue. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed on these differentially expressed mRNAs and miRNA-mediated target genes of lncRNAs and circRNAs. Furthermore, we used a multi-step computational framework and several bioinformatics methods to construct a ceRNA network combining mRNAs, miRNAs, lncRNAs and circRNA, based on co-expression analysis between the differentially expressed RNAs. We identified that plenty of lncRNAs, CircRNAs and their downstream target genes in the ceRNA network are related to glutamatergic synapse, suggesting that glutamate metabolism is involved in glioma biological functions. Our results will accelerate the understanding of tumorigenesis, cancer progression and even therapeutic targeting in glioblastoma.

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Funding

This study was funded by Sichuan province science and technology support Plan Nos. 2012S20152 and 0040205301911.

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Author notes

  1. Yang Yuan and Li Jaoming have contributed equally to this work, should be considered as co-first authors.

Authors and Affiliations

  1. Department of Neurosurgery, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan, China

    Yang Yuan, Li Jiaoming, Wang Xiang, Liu Yanhui, Jiang Shu & Mao Qing

  2. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, China

    Gou Maling

Authors
  1. Yang Yuan
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  2. Li Jiaoming
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  3. Wang Xiang
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  4. Liu Yanhui
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  5. Jiang Shu
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  6. Gou Maling
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  7. Mao Qing
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Correspondence to Jiang Shu or Mao Qing.

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Yuan, Y., Jiaoming, L., Xiang, W. et al. Analyzing the interactions of mRNAs, miRNAs, lncRNAs and circRNAs to predict competing endogenous RNA networks in glioblastoma. J Neurooncol 137, 493–502 (2018). https://doi.org/10.1007/s11060-018-2757-0

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  • DOI: https://doi.org/10.1007/s11060-018-2757-0

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