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Published in: Neurosurgical Review 1/2021

01-02-2021 | Glioblastoma | Original Article

Identification of N6-methyladenosine-related lncRNAs for patients with primary glioblastoma

Authors: Wen Wang, Junsheng Li, Fa Lin, Jia Guo, Jizong Zhao

Published in: Neurosurgical Review | Issue 1/2021

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Abstract

To investigate the m6a-related long non-coding RNAs (lncRNAs) that may be exploited as potential biomarkers in primary glioblastoma (pGBM), a cohort of 268 glioma samples from GSE16011 dataset was included for discovery. The Chinese Glioma Genome Atlas (CGGA) microarray and RNA sequencing databases were used for validation. Bioinformatic analyses were performed using the R software. The m6a-lncRNA co-expression networks were constructed, and four m6a-related lncRNAs (MIR9-3HG, LINC00900, MIR155HG, and LINC00515) were identified in pGBM patients on the univariate Cox regression analysis. Patients in the low-risk group had longer overall survival (OS) and progression-free survival (PFS) than those in the high-risk group (P = 0.0025, P = 0.0070). Moreover, the high-risk group displayed older age, isocitrate dehydrogenase (IDH) wild-type, classical and mesenchymal TCGA subtype, and G3 CGGA subtype. Distinct m6a status was identified according to histologic grade and two groups (low-risk and high-risk). Functional annotation showed that differentially expressed genes between the two groups were enriched in immune response, apoptosis, cell adhesion, negative regulation of transcription, negative regulation of RNA metabolic process, and regulation of RNA metabolic process. We profiled the m6a status in glioma and identified four m6a-related prognostic lncRNAs for pGBMs.
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Literature
1.
go back to reference Yang P, Wang Y, Peng X, You G, Zhang W, Yan W, Bao Z, Wang Y, Qiu X, Jiang T (2013) Management and survival rates in patients with glioma in China (2004-2010): a retrospective study from a single-institution. J Neuro-Oncol 113:259–266CrossRef Yang P, Wang Y, Peng X, You G, Zhang W, Yan W, Bao Z, Wang Y, Qiu X, Jiang T (2013) Management and survival rates in patients with glioma in China (2004-2010): a retrospective study from a single-institution. J Neuro-Oncol 113:259–266CrossRef
2.
go back to reference Yang Y, Hsu PJ, Chen YS, Yang YG (2018) Dynamic transcriptomic m(6)A decoration: writers, erasers, readers and functions in RNA metabolism. Cell Res 28:616–624CrossRef Yang Y, Hsu PJ, Chen YS, Yang YG (2018) Dynamic transcriptomic m(6)A decoration: writers, erasers, readers and functions in RNA metabolism. Cell Res 28:616–624CrossRef
3.
go back to reference Weng H, Huang H, Wu H et al (2018) METTL14 inhibits hematopoietic stem/progenitor differentiation and promotes leukemogenesis via mRNA m(6)A modification. Cell Stem Cell 22:191–205 e199CrossRef Weng H, Huang H, Wu H et al (2018) METTL14 inhibits hematopoietic stem/progenitor differentiation and promotes leukemogenesis via mRNA m(6)A modification. Cell Stem Cell 22:191–205 e199CrossRef
4.
go back to reference Bansal H, Yihua Q, Iyer SP, Ganapathy S, Proia DA, Penalva LO, Uren PJ, Suresh U, Carew JS, Karnad AB, Weitman S, Tomlinson GE, Rao MK, Kornblau SM, Bansal S (2014) WTAP is a novel oncogenic protein in acute myeloid leukemia. Leukemia 28:1171–1174CrossRef Bansal H, Yihua Q, Iyer SP, Ganapathy S, Proia DA, Penalva LO, Uren PJ, Suresh U, Carew JS, Karnad AB, Weitman S, Tomlinson GE, Rao MK, Kornblau SM, Bansal S (2014) WTAP is a novel oncogenic protein in acute myeloid leukemia. Leukemia 28:1171–1174CrossRef
5.
go back to reference Cui Q, Shi H, Ye P et al (2017) m(6)A RNA methylation regulates the self-renewal and tumorigenesis of glioblastoma stem cells. Cell Rep 18:2622–2634CrossRef Cui Q, Shi H, Ye P et al (2017) m(6)A RNA methylation regulates the self-renewal and tumorigenesis of glioblastoma stem cells. Cell Rep 18:2622–2634CrossRef
6.
go back to reference Liu J, Ren D, Du Z, Wang H, Zhang H, Jin Y (2018) m(6)A demethylase FTO facilitates tumor progression in lung squamous cell carcinoma by regulating MZF1 expression. Biochem Biophys Res Commun 502:456–464CrossRef Liu J, Ren D, Du Z, Wang H, Zhang H, Jin Y (2018) m(6)A demethylase FTO facilitates tumor progression in lung squamous cell carcinoma by regulating MZF1 expression. Biochem Biophys Res Commun 502:456–464CrossRef
7.
go back to reference Zhang S, Zhao BS, Zhou A et al (2017) m(6)A demethylase ALKBH5 maintains tumorigenicity of glioblastoma stem-like cells by sustaining FOXM1 expression and cell proliferation program. Cancer Cell 31:591–606 e596CrossRef Zhang S, Zhao BS, Zhou A et al (2017) m(6)A demethylase ALKBH5 maintains tumorigenicity of glioblastoma stem-like cells by sustaining FOXM1 expression and cell proliferation program. Cancer Cell 31:591–606 e596CrossRef
8.
go back to reference Patil DP, Chen CK, Pickering BF et al (2016) m(6)A RNA methylation promotes XIST-mediated transcriptional repression. Nature 537:369–373CrossRef Patil DP, Chen CK, Pickering BF et al (2016) m(6)A RNA methylation promotes XIST-mediated transcriptional repression. Nature 537:369–373CrossRef
9.
go back to reference Zhao X, Chen Y, Mao Q, Jiang X, Jiang W, Chen J, Xu W, Zhong L, Sun X (2018) Overexpression of YTHDF1 is associated with poor prognosis in patients with hepatocellular carcinoma. Cancer Biomark 21:859–868CrossRef Zhao X, Chen Y, Mao Q, Jiang X, Jiang W, Chen J, Xu W, Zhong L, Sun X (2018) Overexpression of YTHDF1 is associated with poor prognosis in patients with hepatocellular carcinoma. Cancer Biomark 21:859–868CrossRef
10.
go back to reference Bian EB, Li J, Xie YS, Zong G, Li J, Zhao B (2015) lncRNAs: new players in gliomas, with special emphasis on the interaction of lncRNAs with EZH2. J Cell Physiol 230:496–503CrossRef Bian EB, Li J, Xie YS, Zong G, Li J, Zhao B (2015) lncRNAs: new players in gliomas, with special emphasis on the interaction of lncRNAs with EZH2. J Cell Physiol 230:496–503CrossRef
11.
go back to reference Sun Y, Wang Z, Zhou D (2013) Long non-coding RNAs as potential biomarkers and therapeutic targets for gliomas. Med Hypotheses 81:319–321CrossRef Sun Y, Wang Z, Zhou D (2013) Long non-coding RNAs as potential biomarkers and therapeutic targets for gliomas. Med Hypotheses 81:319–321CrossRef
12.
go back to reference Zhang XQ, Leung GK (2014) Long non-coding RNAs in glioma: functional roles and clinical perspectives. Neurochem Int 77:78–85CrossRef Zhang XQ, Leung GK (2014) Long non-coding RNAs in glioma: functional roles and clinical perspectives. Neurochem Int 77:78–85CrossRef
13.
go back to reference Wang P, Ren Z, Sun P (2012) Overexpression of the long non-coding RNA MEG3 impairs in vitro glioma cell proliferation. J Cell Biochem 113:1868–1874CrossRef Wang P, Ren Z, Sun P (2012) Overexpression of the long non-coding RNA MEG3 impairs in vitro glioma cell proliferation. J Cell Biochem 113:1868–1874CrossRef
14.
go back to reference Wang Q, Zhang J, Liu Y, Zhang W, Zhou J, Duan R, Pu P, Kang C, Han L (2016) A novel cell cycle-associated lncRNA, HOXA11-AS, is transcribed from the 5-prime end of the HOXA transcript and is a biomarker of progression in glioma. Cancer Lett 373:251–259CrossRef Wang Q, Zhang J, Liu Y, Zhang W, Zhou J, Duan R, Pu P, Kang C, Han L (2016) A novel cell cycle-associated lncRNA, HOXA11-AS, is transcribed from the 5-prime end of the HOXA transcript and is a biomarker of progression in glioma. Cancer Lett 373:251–259CrossRef
15.
go back to reference Han Y, Wu Z, Wu T, Huang Y, Cheng Z, Li X, Sun T, Xie X, Zhou Y, du Z (2016) Tumor-suppressive function of long noncoding RNA MALAT1 in glioma cells by downregulation of MMP2 and inactivation of ERK/MAPK signaling. Cell Death Dis 7:e2123CrossRef Han Y, Wu Z, Wu T, Huang Y, Cheng Z, Li X, Sun T, Xie X, Zhou Y, du Z (2016) Tumor-suppressive function of long noncoding RNA MALAT1 in glioma cells by downregulation of MMP2 and inactivation of ERK/MAPK signaling. Cell Death Dis 7:e2123CrossRef
16.
go back to reference Ni W, Yao S, Zhou Y, Liu Y, Huang P, Zhou A, Liu J, Che L, Li J (2019) Long noncoding RNA GAS5 inhibits progression of colorectal cancer by interacting with and triggering YAP phosphorylation and degradation and is negatively regulated by the m(6)A reader YTHDF3. Mol Cancer 18:143CrossRef Ni W, Yao S, Zhou Y, Liu Y, Huang P, Zhou A, Liu J, Che L, Li J (2019) Long noncoding RNA GAS5 inhibits progression of colorectal cancer by interacting with and triggering YAP phosphorylation and degradation and is negatively regulated by the m(6)A reader YTHDF3. Mol Cancer 18:143CrossRef
17.
go back to reference Wu Y, Yang X, Chen Z et al (2019) m(6)A-induced lncRNA RP11 triggers the dissemination of colorectal cancer cells via upregulation of Zeb1. Mol Cancer 18:87CrossRef Wu Y, Yang X, Chen Z et al (2019) m(6)A-induced lncRNA RP11 triggers the dissemination of colorectal cancer cells via upregulation of Zeb1. Mol Cancer 18:87CrossRef
18.
go back to reference He Y, Hu H, Wang Y, Yuan H, Lu Z, Wu P, Liu D, Tian L, Yin J, Jiang K, Miao Y (2018) ALKBH5 inhibits pancreatic cancer motility by decreasing long non-coding RNA KCNK15-AS1 methylation. Cell Physiol Biochem 48:838–846CrossRef He Y, Hu H, Wang Y, Yuan H, Lu Z, Wu P, Liu D, Tian L, Yin J, Jiang K, Miao Y (2018) ALKBH5 inhibits pancreatic cancer motility by decreasing long non-coding RNA KCNK15-AS1 methylation. Cell Physiol Biochem 48:838–846CrossRef
19.
go back to reference Zhang X, Sun S, Pu JK, Tsang AC, Lee D, Man VO, Lui WM, Wong ST, Leung GK (2012) Long non-coding RNA expression profiles predict clinical phenotypes in glioma. Neurobiol Dis 48:1–8CrossRef Zhang X, Sun S, Pu JK, Tsang AC, Lee D, Man VO, Lui WM, Wong ST, Leung GK (2012) Long non-coding RNA expression profiles predict clinical phenotypes in glioma. Neurobiol Dis 48:1–8CrossRef
20.
go back to reference Wang Y, Li Y, Yue M et al (2018) Publisher correction: N(6)-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications. Nat Neurosci Wang Y, Li Y, Yue M et al (2018) Publisher correction: N(6)-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications. Nat Neurosci
21.
go back to reference Michelhaugh SK, Lipovich L, Blythe J, Jia H, Kapatos G, Bannon MJ (2011) Mining Affymetrix microarray data for long non-coding RNAs: altered expression in the nucleus accumbens of heroin abusers. J Neurochem 116:459–466CrossRef Michelhaugh SK, Lipovich L, Blythe J, Jia H, Kapatos G, Bannon MJ (2011) Mining Affymetrix microarray data for long non-coding RNAs: altered expression in the nucleus accumbens of heroin abusers. J Neurochem 116:459–466CrossRef
22.
go back to reference Johnson R (2012) Long non-coding RNAs in Huntington’s disease neurodegeneration. Neurobiol Dis 46:245–254CrossRef Johnson R (2012) Long non-coding RNAs in Huntington’s disease neurodegeneration. Neurobiol Dis 46:245–254CrossRef
23.
go back to reference Cai J, Zhang W, Yang P, Wang Y, Li M, Zhang C, Wang Z, Hu H, Liu Y, Li Q, Wen J, Sun B, Wang X, Jiang T, Jiang C (2015) Identification of a 6-cytokine prognostic signature in patients with primary glioblastoma harboring M2 microglia/macrophage phenotype relevance. PLoS One 10:e0126022CrossRef Cai J, Zhang W, Yang P, Wang Y, Li M, Zhang C, Wang Z, Hu H, Liu Y, Li Q, Wen J, Sun B, Wang X, Jiang T, Jiang C (2015) Identification of a 6-cytokine prognostic signature in patients with primary glioblastoma harboring M2 microglia/macrophage phenotype relevance. PLoS One 10:e0126022CrossRef
24.
go back to reference Bao ZS, Li MY, Wang JY, Zhang CB, Wang HJ, Yan W, Liu YW, Zhang W, Chen L, Jiang T (2014) Prognostic value of a nine-gene signature in glioma patients based on mRNA expression profiling. CNS Neurosci Ther 20:112–118CrossRef Bao ZS, Li MY, Wang JY, Zhang CB, Wang HJ, Yan W, Liu YW, Zhang W, Chen L, Jiang T (2014) Prognostic value of a nine-gene signature in glioma patients based on mRNA expression profiling. CNS Neurosci Ther 20:112–118CrossRef
25.
go back to reference Zhang CB, Zhu P, Yang P, Cai JQ, Wang ZL, Li QB, Bao ZS, Zhang W, Jiang T (2015) Identification of high risk anaplastic gliomas by a diagnostic and prognostic signature derived from mRNA expression profiling. Oncotarget 6:36643–36651CrossRef Zhang CB, Zhu P, Yang P, Cai JQ, Wang ZL, Li QB, Bao ZS, Zhang W, Jiang T (2015) Identification of high risk anaplastic gliomas by a diagnostic and prognostic signature derived from mRNA expression profiling. Oncotarget 6:36643–36651CrossRef
26.
go back to reference Lossos IS, Czerwinski DK, Alizadeh AA, Wechser MA, Tibshirani R, Botstein D, Levy R (2004) Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes. N Engl J Med 350:1828–1837CrossRef Lossos IS, Czerwinski DK, Alizadeh AA, Wechser MA, Tibshirani R, Botstein D, Levy R (2004) Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes. N Engl J Med 350:1828–1837CrossRef
27.
go back to reference Zhang W, Zhang J, Yan W, You G, Bao Z, Li S, Kang C, Jiang C, You Y, Zhang Y, Chen CC, Song SW, Jiang T (2013) Whole-genome microRNA expression profiling identifies a 5-microRNA signature as a prognostic biomarker in Chinese patients with primary glioblastoma multiforme. Cancer 119:814–824CrossRef Zhang W, Zhang J, Yan W, You G, Bao Z, Li S, Kang C, Jiang C, You Y, Zhang Y, Chen CC, Song SW, Jiang T (2013) Whole-genome microRNA expression profiling identifies a 5-microRNA signature as a prognostic biomarker in Chinese patients with primary glioblastoma multiforme. Cancer 119:814–824CrossRef
28.
go back to reference Wang W, Yang F, Zhang L, Chen J, Zhao Z, Wang H, Wu F, Liang T, Yan X, Li J, Lan Q, Wang J, Zhao J (2016) LncRNA profile study reveals four-lncRNA signature associated with the prognosis of patients with anaplastic gliomas. Oncotarget 7:77225–77236CrossRef Wang W, Yang F, Zhang L, Chen J, Zhao Z, Wang H, Wu F, Liang T, Yan X, Li J, Lan Q, Wang J, Zhao J (2016) LncRNA profile study reveals four-lncRNA signature associated with the prognosis of patients with anaplastic gliomas. Oncotarget 7:77225–77236CrossRef
29.
go back to reference Wang W, Zhang L, Liu W, Zhu Q, Lan Q, Zhao J (2016) Antiplatelet agents for the secondary prevention of ischemic stroke or transient ischemic attack: a network meta-analysis. J Stroke Cerebrovasc Dis 25:1081–1089CrossRef Wang W, Zhang L, Liu W, Zhu Q, Lan Q, Zhao J (2016) Antiplatelet agents for the secondary prevention of ischemic stroke or transient ischemic attack: a network meta-analysis. J Stroke Cerebrovasc Dis 25:1081–1089CrossRef
30.
go back to reference Dai D, Wang H, Zhu L, Jin H, Wang X (2018) N6-methyladenosine links RNA metabolism to cancer progression. Cell Death Dis 9:124CrossRef Dai D, Wang H, Zhu L, Jin H, Wang X (2018) N6-methyladenosine links RNA metabolism to cancer progression. Cell Death Dis 9:124CrossRef
31.
go back to reference Nikkanen J, Landoni JC, Balboa D, Haugas M, Partanen J, Paetau A, Isohanni P, Brilhante V, Suomalainen A (2018) A complex genomic locus drives mtDNA replicase POLG expression to its disease-related nervous system regions. EMBO Mol Med 10:13–21CrossRef Nikkanen J, Landoni JC, Balboa D, Haugas M, Partanen J, Paetau A, Isohanni P, Brilhante V, Suomalainen A (2018) A complex genomic locus drives mtDNA replicase POLG expression to its disease-related nervous system regions. EMBO Mol Med 10:13–21CrossRef
32.
go back to reference Jia L, Wu D, Wang Y, You W, Wang Z, Xiao L, Cai G, Xu Z, Zou C, Wang F, Teoh JY, Ng CF, Yu S, Chan FL (2018) Orphan nuclear receptor TLX contributes to androgen insensitivity in castration-resistant prostate cancer via its repression of androgen receptor transcription. Oncogene 37:3340–3355CrossRef Jia L, Wu D, Wang Y, You W, Wang Z, Xiao L, Cai G, Xu Z, Zou C, Wang F, Teoh JY, Ng CF, Yu S, Chan FL (2018) Orphan nuclear receptor TLX contributes to androgen insensitivity in castration-resistant prostate cancer via its repression of androgen receptor transcription. Oncogene 37:3340–3355CrossRef
33.
go back to reference Thiele JA, Hosek P, Kralovcova E et al (2018) lncRNAs in non-malignant tissue have prognostic value in colorectal cancer. Int J Mol Sci 19 Thiele JA, Hosek P, Kralovcova E et al (2018) lncRNAs in non-malignant tissue have prognostic value in colorectal cancer. Int J Mol Sci 19
34.
go back to reference Song J, Peng J, Zhu C, Bai G, Liu Y, Zhu J, Liu J (2018) Identification and validation of two novel prognostic lncRNAs in kidney renal clear cell carcinoma. Cell Physiol Biochem 48:2549–2562CrossRef Song J, Peng J, Zhu C, Bai G, Liu Y, Zhu J, Liu J (2018) Identification and validation of two novel prognostic lncRNAs in kidney renal clear cell carcinoma. Cell Physiol Biochem 48:2549–2562CrossRef
35.
go back to reference Wu X, Wang Y, Yu T, Nie E, Hu Q, Wu W, Zhi T, Jiang K, Wang X, Lu X, Li H, Liu N, Zhang J, You Y (2017) Blocking MIR155HG/miR-155 axis inhibits mesenchymal transition in glioma. Neuro-Oncology 19:1195–1205CrossRef Wu X, Wang Y, Yu T, Nie E, Hu Q, Wu W, Zhi T, Jiang K, Wang X, Lu X, Li H, Liu N, Zhang J, You Y (2017) Blocking MIR155HG/miR-155 axis inhibits mesenchymal transition in glioma. Neuro-Oncology 19:1195–1205CrossRef
36.
go back to reference Balasubramaniyan V, Bhat KP (2017) Targeting MIR155HG in glioma: a novel approach. Neuro-Oncology 19:1152–1153CrossRef Balasubramaniyan V, Bhat KP (2017) Targeting MIR155HG in glioma: a novel approach. Neuro-Oncology 19:1152–1153CrossRef
37.
go back to reference Lu D, Yang C, Zhang Z, Cong Y, Xiao M (2018) Knockdown of Linc00515 inhibits multiple myeloma autophagy and chemoresistance by upregulating miR-140-5p and downregulating ATG14. Cell Physiol Biochem 48:2517–2527CrossRef Lu D, Yang C, Zhang Z, Cong Y, Xiao M (2018) Knockdown of Linc00515 inhibits multiple myeloma autophagy and chemoresistance by upregulating miR-140-5p and downregulating ATG14. Cell Physiol Biochem 48:2517–2527CrossRef
38.
go back to reference Zheng ZG, Xu H, Suo SS et al (2016) The essential role of H19 contributing to cisplatin resistance by regulating glutathione metabolism in high-grade serous ovarian cancer. Sci Rep 6:26093CrossRef Zheng ZG, Xu H, Suo SS et al (2016) The essential role of H19 contributing to cisplatin resistance by regulating glutathione metabolism in high-grade serous ovarian cancer. Sci Rep 6:26093CrossRef
Metadata
Title
Identification of N6-methyladenosine-related lncRNAs for patients with primary glioblastoma
Authors
Wen Wang
Junsheng Li
Fa Lin
Jia Guo
Jizong Zhao
Publication date
01-02-2021
Publisher
Springer Berlin Heidelberg
Published in
Neurosurgical Review / Issue 1/2021
Print ISSN: 0344-5607
Electronic ISSN: 1437-2320
DOI
https://doi.org/10.1007/s10143-020-01238-x

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