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Published in: Journal of Neuro-Oncology 3/2018

01-05-2018 | Laboratory Investigation

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

Authors: Yang Yuan, Li Jiaoming, Wang Xiang, Liu Yanhui, Jiang Shu, Gou Maling, Mao Qing

Published in: Journal of Neuro-Oncology | Issue 3/2018

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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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Literature
1.
go back to reference Venkatesh T, Suresh PS, Tsutsumi R (2015) Non-coding RNAs: functions and applications in endocrine-related cancer. Mol Cell Endocrinol 416(1):1–21 Venkatesh T, Suresh PS, Tsutsumi R (2015) Non-coding RNAs: functions and applications in endocrine-related cancer. Mol Cell Endocrinol 416(1):1–21
2.
go back to reference Sumazin P et al (2011) An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma. Can Res 147(2):370–381 Sumazin P et al (2011) An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma. Can Res 147(2):370–381
3.
go back to reference Chen Y, Li C, Tan C, Liu X (2016) Circular RNAs: a new frontier in the study of human diseases. J Med Genet 53(6):359–365CrossRefPubMed Chen Y, Li C, Tan C, Liu X (2016) Circular RNAs: a new frontier in the study of human diseases. J Med Genet 53(6):359–365CrossRefPubMed
4.
go back to reference Li JH, Liu S, Zhou H, Qu LH, Yang JH (2013) Starbase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale clip-seq data. Nucleic Acids Res 42(D1): 92–97CrossRef Li JH, Liu S, Zhou H, Qu LH, Yang JH (2013) Starbase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale clip-seq data. Nucleic Acids Res 42(D1): 92–97CrossRef
5.
go back to reference Ju YP, Lee JE, Park et al (2014) Roles of long non-coding RNAs on tumorigenesis and glioma development. Brain Tumor Res Treat (1):1–6 Ju YP, Lee JE, Park et al (2014) Roles of long non-coding RNAs on tumorigenesis and glioma development. Brain Tumor Res Treat (1):1–6
9.
go back to reference Thomson DW, Dinger ME (2016) Endogenous microRNA sponges: evidence and controversy. Nat Rev Genet 17(5):272 –283CrossRefPubMed Thomson DW, Dinger ME (2016) Endogenous microRNA sponges: evidence and controversy. Nat Rev Genet 17(5):272 –283CrossRefPubMed
10.
go back to reference Li Y, Zheng Q, Bao C, Li S, Guo W, Zhao J et al (2015) Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res 25(8):981CrossRefPubMedPubMedCentral Li Y, Zheng Q, Bao C, Li S, Guo W, Zhao J et al (2015) Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res 25(8):981CrossRefPubMedPubMedCentral
11.
go back to reference Shao T, Wu A, Chen J, Chen H, Lu J, Bai J et al (2015) Identification of module biomarkers from the dysregulated ceRNA-ceRNA interaction network in lung adenocarcinoma. Mol Biosyst 11(11):3048–3058CrossRefPubMed Shao T, Wu A, Chen J, Chen H, Lu J, Bai J et al (2015) Identification of module biomarkers from the dysregulated ceRNA-ceRNA interaction network in lung adenocarcinoma. Mol Biosyst 11(11):3048–3058CrossRefPubMed
12.
go back to reference Dou C, Cao Z, Yang B, Ding N, Hou T, Luo F et al (2016) Changing expression profiles of lncRNAs, mRNAs, circRNAs and miRNAs during osteoclastogenesis. Sci Rep 6:21499CrossRefPubMedPubMedCentral Dou C, Cao Z, Yang B, Ding N, Hou T, Luo F et al (2016) Changing expression profiles of lncRNAs, mRNAs, circRNAs and miRNAs during osteoclastogenesis. Sci Rep 6:21499CrossRefPubMedPubMedCentral
13.
go back to reference Wang PF, Liu N, Song HW, Yao K, Jiang T, Li SW et al (2016) Idh-1r132h mutation status in diffuse glioma patients: implications for classification. Oncotarget 7(21):31393–31400PubMedPubMedCentral Wang PF, Liu N, Song HW, Yao K, Jiang T, Li SW et al (2016) Idh-1r132h mutation status in diffuse glioma patients: implications for classification. Oncotarget 7(21):31393–31400PubMedPubMedCentral
14.
go back to reference Zou P, Xu H, Chen P, Yan Q, Zhao L, Zhao P et al (2013) Idh1/idh2 mutations define the prognosis and molecular profiles of patients with gliomas: a meta-analysis. PLoS ONE 8(7):e68782–e68782CrossRefPubMedPubMedCentral Zou P, Xu H, Chen P, Yan Q, Zhao L, Zhao P et al (2013) Idh1/idh2 mutations define the prognosis and molecular profiles of patients with gliomas: a meta-analysis. PLoS ONE 8(7):e68782–e68782CrossRefPubMedPubMedCentral
15.
go back to reference Li Y, Wang Z, Wang Y, Zhao Z, Zhang J, Lu J et al (2016) Identification and characterization of lncRNA mediated transcriptional dysregulation dictates lncRNA roles in glioblastoma. Oncotarget 19(29):45027–45041 Li Y, Wang Z, Wang Y, Zhao Z, Zhang J, Lu J et al (2016) Identification and characterization of lncRNA mediated transcriptional dysregulation dictates lncRNA roles in glioblastoma. Oncotarget 19(29):45027–45041
16.
go back to reference Han L, Zhang K, Shi Z, Zhang J et al (2012) LncRNA profile of glioblastoma reveals the potential role of lncRNAs, in contributing to glioblastoma pathogenesis. Int J Oncol 40(6):2004–2012PubMed Han L, Zhang K, Shi Z, Zhang J et al (2012) LncRNA profile of glioblastoma reveals the potential role of lncRNAs, in contributing to glioblastoma pathogenesis. Int J Oncol 40(6):2004–2012PubMed
17.
go back to reference Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A et al (2013) String v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res 41(Database issue):808–815 Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A et al (2013) String v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res 41(Database issue):808–815
18.
go back to reference Kanehisa M, Araki M, Goto S et al (2008) Kegg for linking genomes to life and the environment. Nucleic Acids Res 36(1):d480–d484 Kanehisa M, Araki M, Goto S et al (2008) Kegg for linking genomes to life and the environment. Nucleic Acids Res 36(1):d480–d484
19.
go back to reference Wagle N, Berger MF, Davis MJ, Blumenstiel B, Defelice M, Pochanard P et al (2012) High-throughput detection of actionable genomic alterations in clinical tumor samples by targeted, massively parallel sequencing. Cancer Discov 2(1):82–93CrossRefPubMed Wagle N, Berger MF, Davis MJ, Blumenstiel B, Defelice M, Pochanard P et al (2012) High-throughput detection of actionable genomic alterations in clinical tumor samples by targeted, massively parallel sequencing. Cancer Discov 2(1):82–93CrossRefPubMed
20.
go back to reference Langmead B, Trapnell C, Pop M, Salzberg SL (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10(3):1–10CrossRef Langmead B, Trapnell C, Pop M, Salzberg SL (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10(3):1–10CrossRef
22.
go back to reference Mao BX, Cai T, Olyarchuk J, Wei (2005) L: Automated genome annotation and pathway identification using the KEGG orthology (KO) as a controlled vocabulary. Bioinformatics 21(19):3787–3793CrossRefPubMed Mao BX, Cai T, Olyarchuk J, Wei (2005) L: Automated genome annotation and pathway identification using the KEGG orthology (KO) as a controlled vocabulary. Bioinformatics 21(19):3787–3793CrossRefPubMed
23.
go back to reference Mortazavi A, Williams BA, Mccue K, Schaeffer L, Wold B (2008) Mapping and quantifying mammalian transcriptomes by RNA-seq. Nat Methods 5(7):621–628CrossRefPubMed Mortazavi A, Williams BA, Mccue K, Schaeffer L, Wold B (2008) Mapping and quantifying mammalian transcriptomes by RNA-seq. Nat Methods 5(7):621–628CrossRefPubMed
24.
go back to reference Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, van Baren MJ, Salzberg SL, Wold BJ, Pachter L (2010) Transcript assembly and quantification by RNA-seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol 28(5):511–515CrossRefPubMedPubMedCentral Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, van Baren MJ, Salzberg SL, Wold BJ, Pachter L (2010) Transcript assembly and quantification by RNA-seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol 28(5):511–515CrossRefPubMedPubMedCentral
26.
go back to reference Jin M, Zhang T, Liu C, Badeaux M et al (2014) MiRNA-128 suppresses prostate cancer by inhibiting BMI-1 to inhibit tumor-initiating cells. Cancer Res 74(15):4183–4195CrossRefPubMedPubMedCentral Jin M, Zhang T, Liu C, Badeaux M et al (2014) MiRNA-128 suppresses prostate cancer by inhibiting BMI-1 to inhibit tumor-initiating cells. Cancer Res 74(15):4183–4195CrossRefPubMedPubMedCentral
27.
go back to reference Cheng CJ, Bahal R, Babar IA et al (2015) MicroRNA silencing for cancer therapy targeted to the tumour microenvironment. Nature 518(7537):107–110CrossRefPubMed Cheng CJ, Bahal R, Babar IA et al (2015) MicroRNA silencing for cancer therapy targeted to the tumour microenvironment. Nature 518(7537):107–110CrossRefPubMed
28.
go back to reference Tay Y, Kats L, Salmena L, Weiss D et al (2011) Coding-independent regulation of the tumor suppressor pten by competing endogenous mRNAs. Cell 147(2):344–357CrossRefPubMedPubMedCentral Tay Y, Kats L, Salmena L, Weiss D et al (2011) Coding-independent regulation of the tumor suppressor pten by competing endogenous mRNAs. Cell 147(2):344–357CrossRefPubMedPubMedCentral
29.
go back to reference Yan Y, Zhang L, Jiang Y, Xu T, Mei Q, Wang H et al (2015) LncRNA and mRNA interaction study based on transcriptome profiles reveals potential core genes in the pathogenesis of human glioblastoma multiforme. J Cancer Res Clin Oncol 141(5):827–838CrossRefPubMed Yan Y, Zhang L, Jiang Y, Xu T, Mei Q, Wang H et al (2015) LncRNA and mRNA interaction study based on transcriptome profiles reveals potential core genes in the pathogenesis of human glioblastoma multiforme. J Cancer Res Clin Oncol 141(5):827–838CrossRefPubMed
30.
go back to reference Johnstone KA, Dubose AJ, Futtner CR, Elmore MD, Brannan CI, Resnick JL (2006) A human imprinting centre demonstrates conserved acquisition but diverged maintenance of imprinting in a mouse model for angelman syndrome imprinting defects. Hum Mol Genet 15(3):393–404CrossRefPubMed Johnstone KA, Dubose AJ, Futtner CR, Elmore MD, Brannan CI, Resnick JL (2006) A human imprinting centre demonstrates conserved acquisition but diverged maintenance of imprinting in a mouse model for angelman syndrome imprinting defects. Hum Mol Genet 15(3):393–404CrossRefPubMed
31.
go back to reference Sutherland HF, Wadey R, Mckie JM, Taylor C, Atif U, Johnstone KA et al (1996) Identification of a novel transcript disrupted by a balanced translocation associated with digeorge syndrome. Am J Hum Genet 59(1):23–31PubMedPubMedCentral Sutherland HF, Wadey R, Mckie JM, Taylor C, Atif U, Johnstone KA et al (1996) Identification of a novel transcript disrupted by a balanced translocation associated with digeorge syndrome. Am J Hum Genet 59(1):23–31PubMedPubMedCentral
32.
go back to reference Willingham AT, Schultz PG (2005) A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science 309(5740):1570–1573CrossRefPubMed Willingham AT, Schultz PG (2005) A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science 309(5740):1570–1573CrossRefPubMed
33.
go back to reference Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK et al (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495(7441):384–388CrossRefPubMed Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK et al (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495(7441):384–388CrossRefPubMed
34.
go back to reference Zhao ZJ, Shen J (2015) Circular RNA participates in the carcinogenesis and the malignant behavior of cancer. RNA Biol 4(3):501–589 Zhao ZJ, Shen J (2015) Circular RNA participates in the carcinogenesis and the malignant behavior of cancer. RNA Biol 4(3):501–589
35.
go back to reference Xu H, Guo S, Li W, Yu P (2015) The circular RNA Cdr1as, via miR-7 and its targets, regulates insulin transcription and secretion in islet cells. Sci Rep 5(1):385–393 Xu H, Guo S, Li W, Yu P (2015) The circular RNA Cdr1as, via miR-7 and its targets, regulates insulin transcription and secretion in islet cells. Sci Rep 5(1):385–393
36.
go back to reference Le TD, Zhang J, Liu L, Li J (2016) Computational methods for identifying miRNA sponge interactions. Brief Bioinform 18(4):577–590 Le TD, Zhang J, Liu L, Li J (2016) Computational methods for identifying miRNA sponge interactions. Brief Bioinform 18(4):577–590
37.
go back to reference Cao Y, Wang P, Ning S, Xiao W, Xiao B, Li X (2016) Identification of prognostic biomarkers in glioblastoma using a long non-coding RNA-mediated, competitive endogenous RNA network. Oncotarget 5(27):41737–41747 Cao Y, Wang P, Ning S, Xiao W, Xiao B, Li X (2016) Identification of prognostic biomarkers in glioblastoma using a long non-coding RNA-mediated, competitive endogenous RNA network. Oncotarget 5(27):41737–41747
Metadata
Title
Analyzing the interactions of mRNAs, miRNAs, lncRNAs and circRNAs to predict competing endogenous RNA networks in glioblastoma
Authors
Yang Yuan
Li Jiaoming
Wang Xiang
Liu Yanhui
Jiang Shu
Gou Maling
Mao Qing
Publication date
01-05-2018
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 3/2018
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-018-2757-0

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