Skip to main content
Erschienen in: Tumor Biology 11/2016

08.09.2016 | Original Article

LncRNA and mRNA expression profiles of glioblastoma multiforme (GBM) reveal the potential roles of lncRNAs in GBM pathogenesis

verfasst von: Qi Li, Hongmei Jia, Haowen Li, Chengya Dong, Yajie Wang, Zhongmei Zou

Erschienen in: Tumor Biology | Ausgabe 11/2016

Einloggen, um Zugang zu erhalten

Abstract

Glioblastoma multiforme (GBM) is the most common brain malignancy. Long non-coding RNAs (lncRNAs) are aberrantly expressed in many cancers and are involved in their cell proliferation, apoptosis, angiogenesis, and invasion. The functional roles of lncRNAs in GBM are less known. We analyzed a cohort of exon microarray datasets from The Cancer Genome Atlas. The differently expressed lncRNAs and mRNA were subjected to construct lncRNA-mRNA co-expression network. Probable functions for lncRNAs were predicted according to lncRNA-mRNA network and genomic adjacency by GO and pathway analysis. The expression of lncRNAs and mRNAs in GBM tissues versus normal brain tissues was examined by quantitative reverse transcription polymerase chain reaction. The 398 lncRNAs and 1995 mRNAs were identified as distinctively expressed in GBM. Probable functional roles for 98 lncRNAs were involved in 30 pathways and 32 gene functions related to tumorigenesis, development, and metastasis. The identified sets of key lncRNAs specific to GBM were subsequently verified by experiment in GBM tissues. Our reports predict the biological functions of a multitude of lncRNAs in GBM that could be potential diagnostic and prognostic biomarkers as well as therapeutic targets. Moreover, our research provides a road map for the identification and analysis of lncRNAs in tumors.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114(2):97–109.CrossRefPubMedPubMedCentral Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114(2):97–109.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Omuro A, DeAngelis LM. Glioblastoma and other malignant gliomas: a clinical review. JAMA. 2013;310(17):1842–50.CrossRefPubMed Omuro A, DeAngelis LM. Glioblastoma and other malignant gliomas: a clinical review. JAMA. 2013;310(17):1842–50.CrossRefPubMed
4.
Zurück zum Zitat Bhan A, Mandal SS. Long noncoding RNAs: emerging stars in gene regulation, epigenetics and human disease. ChemMedChem. 2014;9(9):1932–56.CrossRefPubMed Bhan A, Mandal SS. Long noncoding RNAs: emerging stars in gene regulation, epigenetics and human disease. ChemMedChem. 2014;9(9):1932–56.CrossRefPubMed
6.
Zurück zum Zitat Qi P, Du X. The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine. Mod Pathol. 2013;26(2):155–65.CrossRefPubMed Qi P, Du X. The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine. Mod Pathol. 2013;26(2):155–65.CrossRefPubMed
7.
Zurück zum Zitat Wang P, Liu YH, Yao YL, et al. Long non-coding RNA CASC2 suppresses malignancy in human gliomas by miR-21. Cell Signal. 2015;27(2):275–82.CrossRefPubMed Wang P, Liu YH, Yao YL, et al. Long non-coding RNA CASC2 suppresses malignancy in human gliomas by miR-21. Cell Signal. 2015;27(2):275–82.CrossRefPubMed
8.
Zurück zum Zitat Guo H, Wu L, Yang Q, et al. Functional linc-POU3F3 is overexpressed and contributes to tumorigenesis in glioma. Gene. 2014;554:114–9.CrossRefPubMed Guo H, Wu L, Yang Q, et al. Functional linc-POU3F3 is overexpressed and contributes to tumorigenesis in glioma. Gene. 2014;554:114–9.CrossRefPubMed
9.
Zurück zum Zitat Zhang K, Sun X, Zhou X, et al. Long non-coding RNA HOTAIR promotes glioblastoma cell cycle progression in an EZH2 dependent manner. Oncotarget. 2015;6:537–46.PubMed Zhang K, Sun X, Zhou X, et al. Long non-coding RNA HOTAIR promotes glioblastoma cell cycle progression in an EZH2 dependent manner. Oncotarget. 2015;6:537–46.PubMed
10.
Zurück zum Zitat Qin X, Yao J, Geng P, et al. LncRNA TSLC1-AS1 is a novel tumor suppressor in glioma. Int J Clin Exp Pathol. 2014;7:3065–72.PubMedPubMedCentral Qin X, Yao J, Geng P, et al. LncRNA TSLC1-AS1 is a novel tumor suppressor in glioma. Int J Clin Exp Pathol. 2014;7:3065–72.PubMedPubMedCentral
11.
Zurück zum Zitat Yao J, Zhou B, Zhang J, et al. A new tumor suppressor LncRNA ADAMTS9-AS2 is regulated by DNMT1 and inhibits migration of glioma cells. Tumour Biol. 2014;35:7935–44.CrossRefPubMed Yao J, Zhou B, Zhang J, et al. A new tumor suppressor LncRNA ADAMTS9-AS2 is regulated by DNMT1 and inhibits migration of glioma cells. Tumour Biol. 2014;35:7935–44.CrossRefPubMed
13.
Zurück zum Zitat Zhang X, Sun S, Pu JK, et al. Long non-coding RNA expression profiles predict clinical phenotypes in glioma. Neurobiol of Dis. 2012;48(1):1–8.CrossRef Zhang X, Sun S, Pu JK, et al. Long non-coding RNA expression profiles predict clinical phenotypes in glioma. Neurobiol of Dis. 2012;48(1):1–8.CrossRef
14.
Zurück zum Zitat Han L, Zhang K, Shi Z, et al. LncRNA profile of glioblastoma reveals the potential role of lncRNAs in contributing to glioblastoma pathogenesis. Int J Oncol. 2012;40(6):2004–12. Han L, Zhang K, Shi Z, et al. LncRNA profile of glioblastoma reveals the potential role of lncRNAs in contributing to glioblastoma pathogenesis. Int J Oncol. 2012;40(6):2004–12.
15.
Zurück zum Zitat Yan Y, Zhang L, Jiang Y, et al. LncRNA and mRNA interaction study based on transcriptome profiles reveals potential core genes in the pathogenesis of human glioblastoma multiforme. Cancer Res Clin Oncol. 2014;141(5):827–38.CrossRef Yan Y, Zhang L, Jiang Y, et al. LncRNA and mRNA interaction study based on transcriptome profiles reveals potential core genes in the pathogenesis of human glioblastoma multiforme. Cancer Res Clin Oncol. 2014;141(5):827–38.CrossRef
16.
Zurück zum Zitat Gellert P, Ponomareva Y, Braun T, et al. Noncoder: a web interface for exon array-based detection of long non-coding RNAs. Nucleic Acids Res. 2013;41(1):e20.CrossRefPubMed Gellert P, Ponomareva Y, Braun T, et al. Noncoder: a web interface for exon array-based detection of long non-coding RNAs. Nucleic Acids Res. 2013;41(1):e20.CrossRefPubMed
17.
Zurück zum Zitat Zhang JX, Han L, Bao ZS, et al. HOTAIR, a cell cycle-associated long noncoding RNA and a strong predictor of survival, is preferentially expressed in classical and mesenchymal glioma. Neuro-Oncology. 2013;15(12):1595–603.CrossRefPubMedPubMedCentral Zhang JX, Han L, Bao ZS, et al. HOTAIR, a cell cycle-associated long noncoding RNA and a strong predictor of survival, is preferentially expressed in classical and mesenchymal glioma. Neuro-Oncology. 2013;15(12):1595–603.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Benetatos L, Vartholomatos G, Hatzimichael E. MEG3 imprinted gene contribution in tumorigenesis. Int J Cancer. 2011;129(4):773–9.CrossRefPubMed Benetatos L, Vartholomatos G, Hatzimichael E. MEG3 imprinted gene contribution in tumorigenesis. Int J Cancer. 2011;129(4):773–9.CrossRefPubMed
20.
Zurück zum Zitat Pang KC, Frith MC, Mattick JS. Rapid evolution of noncoding RNAs: lack of conservation does not mean lack of function. Trends Genet. 2006;22(1):1–5.CrossRefPubMed Pang KC, Frith MC, Mattick JS. Rapid evolution of noncoding RNAs: lack of conservation does not mean lack of function. Trends Genet. 2006;22(1):1–5.CrossRefPubMed
21.
Zurück zum Zitat Guttman M, Amit I, Garber M, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009;458(7235):223–7.CrossRefPubMedPubMedCentral Guttman M, Amit I, Garber M, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009;458(7235):223–7.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Siepel A, Bejerano G, Pedersen JS, et al. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 2005;15(8):1034–50.CrossRefPubMedPubMedCentral Siepel A, Bejerano G, Pedersen JS, et al. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 2005;15(8):1034–50.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Liao Q, Liu C, Yuan X, et al. Large-scale prediction of long non-coding RNA functions in a coding-non-coding gene co-expression network. Nucleic Acids Res. 2011;39(9):3864–78.CrossRefPubMedPubMedCentral Liao Q, Liu C, Yuan X, et al. Large-scale prediction of long non-coding RNA functions in a coding-non-coding gene co-expression network. Nucleic Acids Res. 2011;39(9):3864–78.CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Pujana MA, Han JD, Starita LM, et al. Network modeling links breast cancer susceptibility and centrosome dysfunction. Nat Genet. 2007;39(11):1338–49.CrossRefPubMed Pujana MA, Han JD, Starita LM, et al. Network modeling links breast cancer susceptibility and centrosome dysfunction. Nat Genet. 2007;39(11):1338–49.CrossRefPubMed
25.
Zurück zum Zitat Stumpf CR, Moreno MV, Olshen AB, Taylor BS, Ruggero D. The transcriptional landscape of the mammalian genome. Science. 2005;309:1559–63.CrossRef Stumpf CR, Moreno MV, Olshen AB, Taylor BS, Ruggero D. The transcriptional landscape of the mammalian genome. Science. 2005;309:1559–63.CrossRef
26.
Zurück zum Zitat Ponjavic J, Oliver PL, Lunter G, et al. Genomic and transcriptional co-localization of protein-coding and long non-coding RNA pairs in the developing brain. PLoS Genet. 2009;5(8):e1000617.CrossRefPubMedPubMedCentral Ponjavic J, Oliver PL, Lunter G, et al. Genomic and transcriptional co-localization of protein-coding and long non-coding RNA pairs in the developing brain. PLoS Genet. 2009;5(8):e1000617.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Hodgson JG, Yeh RF, Ray A, et al. Comparative analyses of gene copy number and mRNA expression in glioblastoma multiforme tumors and xenografts. Neuro-Oncology. 2009;11(5):477–87.CrossRefPubMedPubMedCentral Hodgson JG, Yeh RF, Ray A, et al. Comparative analyses of gene copy number and mRNA expression in glioblastoma multiforme tumors and xenografts. Neuro-Oncology. 2009;11(5):477–87.CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Marucci G, Morandi L, Magrini E, et al. Gene expression profiling in glioblastoma and immunohistochemical evaluation of IGFBP-2 and CDC20. Virchows Arch. 2008;453(6):599–609.CrossRefPubMed Marucci G, Morandi L, Magrini E, et al. Gene expression profiling in glioblastoma and immunohistochemical evaluation of IGFBP-2 and CDC20. Virchows Arch. 2008;453(6):599–609.CrossRefPubMed
29.
Zurück zum Zitat Liu X, Chhipa RR, Pooya S, et al. Discrete mechanisms of mTOR and cell cycle regulation by AMPK agonists independent of AMPK. Proc Natl Acad Sci. 2014;111(4):E435–44.CrossRefPubMedPubMedCentral Liu X, Chhipa RR, Pooya S, et al. Discrete mechanisms of mTOR and cell cycle regulation by AMPK agonists independent of AMPK. Proc Natl Acad Sci. 2014;111(4):E435–44.CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Aoki H, Yokoyama T, Fujiwara K, et al. Phosphorylated Pak1 level in the cytoplasm correlates with shorter survival time in patients with glioblastoma. Clin Cancer Res. 2007;13(22 Pt 1):6603–9.CrossRefPubMed Aoki H, Yokoyama T, Fujiwara K, et al. Phosphorylated Pak1 level in the cytoplasm correlates with shorter survival time in patients with glioblastoma. Clin Cancer Res. 2007;13(22 Pt 1):6603–9.CrossRefPubMed
31.
Zurück zum Zitat Bhattacharya K, Bag AK, Tripathi R, et al. Mahanine, a novel mitochondrial complex-III inhibitor induces G0/G1 arrest through redox alteration-mediated DNA damage response and regresses glioblastoma multiforme. Am J Cancer Res. 2014;4(6):629–47.PubMedPubMedCentral Bhattacharya K, Bag AK, Tripathi R, et al. Mahanine, a novel mitochondrial complex-III inhibitor induces G0/G1 arrest through redox alteration-mediated DNA damage response and regresses glioblastoma multiforme. Am J Cancer Res. 2014;4(6):629–47.PubMedPubMedCentral
32.
Zurück zum Zitat Gao J, Chen T, Liu J, et al. Loss of NECL a novel tumor suppressor, can be restored in glioma by HDAC inhibitor-Trichostatin A through Sp1 binding site. Glia. 2009;57:989–99.CrossRefPubMed Gao J, Chen T, Liu J, et al. Loss of NECL a novel tumor suppressor, can be restored in glioma by HDAC inhibitor-Trichostatin A through Sp1 binding site. Glia. 2009;57:989–99.CrossRefPubMed
33.
Zurück zum Zitat Aronica E, Gorter JA, Ijlst-Keizers H, et al. Expression and functional role of mGluR3 and mGluR5 in human astrocytes and glioma cells: opposite regulation of glutamate transporter proteins. Eur J Neurosci. 2003;17(10):2106–18.CrossRefPubMed Aronica E, Gorter JA, Ijlst-Keizers H, et al. Expression and functional role of mGluR3 and mGluR5 in human astrocytes and glioma cells: opposite regulation of glutamate transporter proteins. Eur J Neurosci. 2003;17(10):2106–18.CrossRefPubMed
34.
Zurück zum Zitat McAvoy S, Ganapathiraju SC, Ducharme-Smith AL, et al. Non-random inactivation of large common fragile site genes in different cancers. Cytogenet Genome Res. 2007;118(2–4):260–9.CrossRefPubMed McAvoy S, Ganapathiraju SC, Ducharme-Smith AL, et al. Non-random inactivation of large common fragile site genes in different cancers. Cytogenet Genome Res. 2007;118(2–4):260–9.CrossRefPubMed
35.
Zurück zum Zitat Wang E, Zhang C, Polavaram N, et al. The role of factor inhibiting HIF (FIH-1) in inhibiting HIF-1 transcriptional activity in glioblastoma multiforme. PLoS One. 2014;9(1):e86102.CrossRefPubMedPubMedCentral Wang E, Zhang C, Polavaram N, et al. The role of factor inhibiting HIF (FIH-1) in inhibiting HIF-1 transcriptional activity in glioblastoma multiforme. PLoS One. 2014;9(1):e86102.CrossRefPubMedPubMedCentral
36.
Zurück zum Zitat Tian B, Zhang Y, Zhang J. Periostin is a new potential prognostic biomarker for glioma. Tumour Biol. 2014;35(6):5877–83.CrossRefPubMed Tian B, Zhang Y, Zhang J. Periostin is a new potential prognostic biomarker for glioma. Tumour Biol. 2014;35(6):5877–83.CrossRefPubMed
37.
Zurück zum Zitat Ruano Y, Mollejo M, Camacho FI, et al. Identification of survival-related genes of the phosphatidylinositol 3′-kinase signaling pathway in glioblastoma multiforme. Cancer. 2008;112(7):1575–84.CrossRefPubMed Ruano Y, Mollejo M, Camacho FI, et al. Identification of survival-related genes of the phosphatidylinositol 3′-kinase signaling pathway in glioblastoma multiforme. Cancer. 2008;112(7):1575–84.CrossRefPubMed
38.
Zurück zum Zitat Rahme GJ, Israel MA. Id4 suppresses MMP2-mediated invasion of glioblastoma-derived cells by direct inactivation of Twist1 function. Oncogene. 2015;34(1):53–62.CrossRefPubMed Rahme GJ, Israel MA. Id4 suppresses MMP2-mediated invasion of glioblastoma-derived cells by direct inactivation of Twist1 function. Oncogene. 2015;34(1):53–62.CrossRefPubMed
39.
Zurück zum Zitat Reed JE, Dunn JR, du Plessis DG, et al. Expression of cellular adhesion molecule ‘OPCML’ is down-regulated in gliomas and other brain tumours. Neuropathol Appl Neurobiol. 2007;33(1):77–85.CrossRefPubMed Reed JE, Dunn JR, du Plessis DG, et al. Expression of cellular adhesion molecule ‘OPCML’ is down-regulated in gliomas and other brain tumours. Neuropathol Appl Neurobiol. 2007;33(1):77–85.CrossRefPubMed
Metadaten
Titel
LncRNA and mRNA expression profiles of glioblastoma multiforme (GBM) reveal the potential roles of lncRNAs in GBM pathogenesis
verfasst von
Qi Li
Hongmei Jia
Haowen Li
Chengya Dong
Yajie Wang
Zhongmei Zou
Publikationsdatum
08.09.2016
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 11/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5299-0

Weitere Artikel der Ausgabe 11/2016

Tumor Biology 11/2016 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.